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1.
Medicina (B.Aires) ; 80(2): 157-161, abr. 2020. ilus
Article in Spanish | LILACS | ID: biblio-1125057

ABSTRACT

Un tercio de la población mundial tiene niveles anormalmente altos de presión arterial, hipertensión, responsable de casi el 50% de las muertes por accidente cerebrovascular y enfermedad coronaria. La sensibilidad a la sal es un factor de riesgo para la morbilidad y mortalidad cardiovascular y también para otras enfermedades. En estudios previos describimos un modelo de hipertensión sal sensible (HSS) en ratas Wistar ovariectomizadas (oVx) adultas. Las ratas oVx son normotensas con ingesta normal de sal (NS, 0.24% de NaCl), pero desarrollan un perfil de HSS con una ingesta elevada de sal (HS, 1% de NaCl). En los estudios en riñón encontramos que el circuito receptor D1 de dopamina, citocromo P450 4A y Na+, K+-ATPasa está alterado por la ausencia de hormonas ováricas, lo que se asocia a menor excreción de sodio e hipertensión arterial. La ingesta HS en ratas oVx también promueve cambios en la expresión de proteínas relacionadas con el transporte de sodio en células mononucleares de sangre periférica, principalmente linfocitos periféricos. Por lo tanto, el transporte de sodio se modifica en varios niveles de la fisiología normal. En estudios recientes observamos que el estradiol aumenta la proliferación y diferenciación de células epiteliales en cultivos de corteza renal humana. Sensibilidad a la sal, inmunidad adaptativa, presión arterial y proliferación de células epiteliales en riñón son fenómenos de gran importancia biológica regulados por estradiol.


Female sex hormones participate in the regulation of blood pressure and renal epithelial proliferation, effects not related to their reproductive function. About one-third of the world's population has abnormally high levels of blood pressure, hypertension, which is responsible for almost 50% of deaths from stroke and coronary heart disease. Salt sensitivity is a risk factor for cardiovascular morbidity and mortality and other diseases as well. We reported a model of salt sensitive hypertension in adult ovariectomized (oVx) Wistar rats. oVx rats are normotensive under normal salt intake (NS, 0.24% NaCl), but upon a high salt intake (HS, 1% NaCl) oVx rats developed a blood pressure profile of salt-sensitive hypertension. Our studies on kidney molecules related to sodium balance found that the circuit dopamine D1-like receptor, cytochrome P450 4A and Na+, K+-ATPase is altered by the absence of ovary hormones which is accompanied by a reduced ability to excrete sodium. In oVx rats HS intake also promotes changes in the expression of proteins related to sodium transport in peripheral blood mononuclear cells, mainly peripheral lymphocytes. Therefore, sodium transport is modified at several levels of normal physiology. Lately, we described that estradiol increases the rate of renal epithelial cell proliferation in primary cultures developed from human renal cortex. Thus, salt sensitivity, adaptive immunity, blood pressure and renal cell proliferation are complex biological responses regulated by female sex hormones.


Subject(s)
Humans , Animals , Female , Rats , Sodium Chloride/metabolism , Estradiol/metabolism , Hypertension/metabolism , Kidney/metabolism , Blood Pressure , Sodium Chloride/adverse effects , Rats, Wistar , Sodium-Potassium-Exchanging ATPase , Cell Proliferation , Hypertension/physiopathology
2.
Rev. chil. cardiol ; 39(1): 66-74, abr. 2020. graf
Article in Spanish | LILACS | ID: biblio-1115452

ABSTRACT

En 31 de diciembre del 2019 la Organización Mundial de la Salud fue informada por las autoridades sanitarias chinas de la aparición de casos de neumonía de origen desconocido en la ciudad de Wuhan en China. El 7 de Enero de 2020, científicos chinos identificaron a un nuevo coronavirus (temporalmente designado como "2019-nCoV") como el agente etiológico de la enfermedad denominada COVID-19. La secuenciación del genoma del nuevo coronavirus mostró gran similitud con el coronavirus (Covid-1 o SARS-CoV) causante del síndrome respiratorio agudo severo (SARS), ocurrido también en China entre los años 2002-2003. Por este motivo, 2019-nCoV se rebautizó como SARS-CoV-2 (Severe Acute Respiratory Syndrome Corona Virus-2) y a la fecha es responsable de la actual y grave pandemia que está ocasionando impactos sanitarios y socio-económicos a escala global. Las investigaciones con SARS-CoV establecieron que este virus ingresa a nuestras células utilizando como receptor a la enzima convertidora de angiotensina tipo 2 (ECA 2 o en inglés ACE-2: "angiotensin converting enzyme type 2"). Dado este antecedente también se confirmó que SARS-CoV-2 también utiliza esta misma enzima ya que no se habla de un mecanismo en si para ingresar a sus células blanco, especialmente a nivel de nuestro sistema respiratorio. ECA-2 es una proteasa integrante del sistema renina angiotensina "alterno o no canónico" con importantes acciones regulatorias sobre los sistemas cardiovascular, renal y pulmonar, entre otros. En este contexto, ha surgido preocupación tanto por clínicos como los propios pacientes respecto al estado de pacientes hipertensos con COVID-19 y su vulnerabilidad a infectarse con SARS-CoV-2 dado que algunos trabajos han planteado que ciertos polimorfismos en el gen ECA-2 asociados a hipertensión arterial podrían determinar una mayor expresión de ECA-2. Además, estudios preclínicos han sugerido que ciertos fármacos antihipertensivos (principalmente, inhibidores de ECA y antagonistas del receptor para angiotensina II subtipo 1) también podrían estimular una mayor expresión de ECA-2. Esta revisión tiene por objetivo presentar y discutir los antecedentes en el estado del arte respecto a esta reciente problemática. El análisis crítico de los presentes antecedentes permite concluir que no existe evidencia clínica sólida que permita afirmar que el uso de medicamentos antihipertensivos genere una mayor vulnerabilidad a la infección con SARS-CoV-2. Por lo tanto no se debe descontinuar su uso en pacientes hipertensos en riesgo de infección a SARS-CoV-2 o que padezcan COVID-19.


In December 2019, a new type of coronavirus emerged in the city of Wuhan, China. This novel virus has unleashed a pandemic that has inflicted a considerable impact on public health and the economy and has therefore become a severe concern worldwide. This new virus -named SARS-CoV-2has been rapidly investigated in order to create knowledge aimed at achieving its control. Comparative studies with SARS-CoV virus, responsible for the 2002-2003 pandemic, suggest that SARS-CoV-2 requires the same receptor to bind and infect cells: angiotensin converting enzyme 2 (ACE-2). This hypothesis has been thoroughly supported by a variety of in vitro research and is currently considered a potential therapeutic target. ACE-2 is part of the counter-regulatory renin-angiotensin system, exerting effects in pulmonary, renal and cardiovascular systems. In this context, concerns have arisen in regards to the vulnerability of hypertensive patients against COVID-19, given that there is evidence that may suggest that polymorphisms associated to hypertension may increase the expression of ACE-2. Moreover, preclinical studies have shown that antihypertensive drugs may increase the expression of this enzyme. In this review article, we present the current state of the art on this polemic topic. Our critical analysis suggest that there is no robust clinical evidence supporting the hypothesis that the use of antihypertensive drugs can increase vulnerability to infection with SARS-CoV-2. Therefore, we recommend that the use of these therapeutic agents should not be discontinued in hypertensive patients in risk to or suffering COVID-19.


Subject(s)
Humans , Pneumonia, Viral/complications , Coronavirus Infections/complications , Hypertension/complications , Hypertension/drug therapy , Antihypertensive Agents/therapeutic use , Pneumonia, Viral/metabolism , Renin-Angiotensin System , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Coronavirus Infections/metabolism , Peptidyl-Dipeptidase A/genetics , Peptidyl-Dipeptidase A/metabolism , Pandemics , Betacoronavirus/metabolism , Hypertension/metabolism
3.
Braz. arch. biol. technol ; 63: e20190403, 2020. tab, graf
Article in English | LILACS | ID: biblio-1132232

ABSTRACT

Abstract Evidence suggests that polymorphisms in the gene encoding a vitamin D receptor might affect blood pressure. The objective of this systematic review was to investigate the association between hypertension and vitamin D receptor (Fok I) gene polymorphism. A literature search was performed according to the PRISMA guidelines using the MEDLINE®/PubMed, Scopus, Cochrane Library CENTRAL, SciELO, and LILACS databases. The quality of case-control or cohort studies and studies based on cross-sectional methodology was evaluated using the Newcastle-Ottawa Scale and the protocol of Loney and coauthors [25], respectively. In this systematic literature search, 215 publications were identified, of which 10 were analyzed, including seven case-control studies, two cross-sectional studies, and one cohort study. The association between Fok I polymorphism and hypertension was reported in 60% of the publications and the risk for hypertension was shown to be related to FF and ff genotypes. In addition, Fok I polymorphism was shown to increase plasma renin activity, which plays an important role in regulating blood pressure. However, no association was observed between Fok I polymorphism and serum vitamin D levels. In conclusion, Fok I polymorphism plays an important role in hypertension.


Subject(s)
Humans , Polymorphism, Genetic/genetics , Receptors, Calcitriol/genetics , Hypertension/metabolism , Risk Factors
4.
Article in English | WPRIM | ID: wpr-880304

ABSTRACT

BACKGROUND@#The absence of thyroid cysts may indicate latent thyroid damage, as demonstrated in our previous study. However, the association between the absence of thyroid cysts and latent functional damage of the thyroid is unknown. At low thyroid hormone productivity, which may be associated with latent functional damage of the thyroid, the association between thyroid-stimulating hormone (TSH) and hypertension might be enhanced. Therefore, we evaluated the association between TSH level and hypertension stratified by thyroid cyst status.@*METHODS@#We conducted a cross-sectional study of 1724 euthyroid Japanese individuals aged 40-74 years who participated in an annual health checkup in 2014.@*RESULTS@#In the study population, 564 and 686 participants had thyroid cysts and hypertension, respectively. A significant positive association was observed between TSH and hypertension in subjects without a thyroid cyst but not in subjects with thyroid cysts. There was a significant positive association between hypertension and TSH in subjects without a thyroid cyst (odds ratio [OR] 1.27; 95% confidence intervals [CI] 1.01, 1.61) but not in subjects with thyroid cysts (OR 0.79; CI 0.57, 1.09) in the model fully adjusted for known confounding factors. The correlation between the TSH and free triiodothyronine (fee T3) levels (simple correlation coefficient [r] = - 0.13, p < 0.01) was stronger in the subjects without thyroid cysts than in those with thyroid cysts (r = - 0.03, p = 0.525).@*CONCLUSIONS@#TSH is positively associated with hypertension only in individuals without thyroid cysts. The correlation between the TSH and free T3 levels was stronger in the subjects without thyroid cysts than in those with thyroid cysts. Therefore, the absence of thyroid cysts could be related to the association between TSH level and hypertension, possibly by indicating that the subjects without thyroid cysts had limited thyroid hormone reserves. Therefore, the absence of thyroid cysts could indicate the latent functional damage of the thyroid.


Subject(s)
Aged , Cross-Sectional Studies , Cysts/etiology , Female , Humans , Hypertension/metabolism , Japan , Male , Middle Aged , Thyroid Diseases/etiology , Thyroid Gland/pathology , Thyrotropin/metabolism
5.
Rev. méd. Chile ; 147(4): 490-498, abr. 2019. tab, graf
Article in Spanish | LILACS | ID: biblio-1014251

ABSTRACT

The renin-angiotensin-aldosterone system modulates volume, sodium and potassium homeostasis. In the setting of a high sodium diet, up to 30% of patients with hypertension have a low or suppressed renin and increased volume. This phenotype of low renin hypertension (LRH) is multifactorial and includes infrequent inherited genetic syndromes, milder phenotypes of classic diseases and environmental exposures. All these conditions have in common a higher cardiovascular risk mediated by the over activation of the mineralocorticoid receptor (MR), present not only in the kidney, but also in vasculature, myocardium and adipocytes. Consequently, the aim of LRH treatment goes beyond the control of blood pressure and requires antagonizing MR with specific pharmacologic agents, pursuing normalization of renin as a clinical objective. Due to the unusual evaluation of renin status by non-endocrinologists and lack of disease awareness, only a minority of hypertensive patients receive this pathophysiologically-driven treatment that should reduce cardiovascular outcomes.


Subject(s)
Humans , Renin-Angiotensin System/physiology , Hypertension/metabolism , Hypertension/therapy , Renin/metabolism , Receptors, Mineralocorticoid/metabolism , Disease Management , Aldosterone/metabolism , Hypertension/physiopathology
6.
Arq. bras. cardiol ; 112(4): 374-380, Apr. 2019. tab
Article in English | LILACS | ID: biblio-1001285

ABSTRACT

Abstract Background: Mercury's deleterious effects are associated with increased cardiovascular risk. Objective: To determine whether chronic exposure to inorganic mercury increases the activity of angiotensin-converting enzyme and its relationship with oxidative stress in several organs and tissues. Methods: We studied male Wistar and spontaneously hypertensive rats (SHR) (3-month-old) exposed or not to HgCl2 for 30 days. At the end of treatment, we investigated the following: changes in body weight, hemodynamic parameters, angiotensin-converting enzyme (ACE) activity and oxidative stress in the heart, aorta, lung, brain and kidney in hypertensive compared to normotensive animals. A value of p < 0.05 was considered significant. Results: Chronic exposure to HgCl2 did not affect weight gain in either group. Systolic blood pressure, measured weekly, did not increase in Wistar rats but showed a small increase in SHR rats. We also observed increases in left ventricular end-diastolic pressure and ACE activity in the plasma and hearts of normotensive rats. In the SHR+Hg group, ACE activity increased in plasma but decreased in kidney, lung, heart, brain and aorta. Oxidative stress was assessed indirectly by malondialdehyde (MDA) production, which increased in Hg-treated rats in both plasma and heart. In the SHR+Hg group, MDA increased in heart and aorta and decreased in lungs and brain. Conclusion: These results suggest that chronic exposure to inorganic mercury aggravates hypertension and produces more expressive changes in ACE activity and oxidative stress in SHRs. Such exposure affects the cardiovascular system, representing a risk factor for the development of cardiovascular disorders in normotensive rats and worsening of pre-existing risks for hypertension.


Resumo Fundamento: Os efeitos deletérios do mercúrio estão associados ao risco cardiovascular aumentado. Objetivo: Determinar se a exposição crônica ao mercúrio inorgânico aumenta a atividade da enzima conversora de angiotensina e sua relação com o estresse oxidativo em vários órgãos e tecidos. Métodos: Estudamos ratos Wistar e ratos espontaneamente hipertensos (SHR) (3 meses de idade) expostos ou não a HgCl2 por 30 dias. Ao final do tratamento, investigamos: alterações de peso, parâmetros hemodinâmicos, atividade da enzima conversora de angiotensina (ECA) e estresse oxidativo no coração, aorta, pulmão, cérebro e rim de animais hipertensos comparados a animais normotensos. Um valor de p < 0,05 foi considerado significativo. Resultados: A exposição crônica ao HgCl2 não afetou o ganho de peso em nenhum dos grupos. A pressão arterial sistólica, medida semanalmente, não aumentou em ratos Wistar, mas mostrou um pequeno aumento nos ratos SHR. Também observamos aumentos na pressão diastólica final do ventrículo esquerdo e na atividade da ECA no plasma e no coração de ratos normotensos. No grupo SHR + Hg, a atividade da ECA aumentou no plasma, mas diminuiu no rim, pulmão, coração, cérebro e aorta. O estresse oxidativo foi avaliado indiretamente pela produção de MDA, que aumentou nos ratos tratados com Hg tanto no plasma quanto no coração. No grupo SHR + Hg, o MDA aumentou no coração e na aorta e diminuiu nos pulmões e no cérebro. Conclusão: Estes resultados sugerem que a exposição crônica ao mercúrio inorgânico agrava a hipertensão e produz mudanças mais expressivas na atividade da ECA e no estresse oxidativo em SHRs. Essa exposição afeta o sistema cardiovascular, representando um fator de risco para o desenvolvimento de distúrbios cardiovasculares em ratos normotensos e para piorar riscos pré-existentes para hipertensão.


Subject(s)
Animals , Male , Peptidyl-Dipeptidase A/drug effects , Oxidative Stress/drug effects , Hypertension/metabolism , Mercury/toxicity , Mercury Poisoning/complications , Aorta/enzymology , Rats, Inbred SHR , Reference Values , Time Factors , Blood Pressure/drug effects , Brain/enzymology , Risk Factors , Rats, Wistar , Peptidyl-Dipeptidase A/analysis , Heart , Hypertension/physiopathology , Kidney/enzymology , Lung/enzymology , Malondialdehyde/blood
7.
Arq. bras. cardiol ; 111(2): 172-179, Aug. 2018. tab, graf
Article in English | LILACS | ID: biblio-950219

ABSTRACT

Abstract Background: Regulation of intracellular calcium (Ca2+) in cardiomyocytes is altered by hypertension; and aerobic exercise brings benefits to hypertensive individuals. Objective: To verify the effects of aerobic exercise training on contractility and intracellular calcium (Ca2+) transients of cardiomyocytes and on the expression of microRNA 214 (miR-214) in the left ventricle of spontaneously hypertensive rats (SHR). Methods: SHR and normotensive Wistar rats of 16 weeks were divided into 4 groups -sedentary hypertensive (SH); trained hypertensive (TH); sedentary normotensive (SN); and trained normotensive (TN). Animals of the TH and TN groups were subjected to treadmill running program, 5 days/week, 1 hour/day at 60-70% of maximum running velocity for 8 weeks. We adopted a p ≤ 0.05 as significance level for all comparisons. Results: Exercise training reduced systolic arterial pressure in hypertensive rats. In normotensive rats, exercise training reduced the time to 50% cell relaxation and the time to peak contraction and increased the time to 50% decay of the intracellular Ca2+ transients. In SHR, exercise increased the amplitude and reduced the time to 50% decay of Ca2+ transients. Exercise training increased the expression of miR-214 in hypertensive rats only. Conclusion: The aerobic training applied in this study increased the availability of intracellular Ca2+ and accelerated the sequestration of these ions in left ventricular myocytes of hypertensive rats, despite increased expression of miR-214 and maintenance of cell contractility.


Resumo Fundamento: A regulação intracelular de cálcio (Ca2+) em cardiomiócitos é alterada pela hipertensão, e o exercício físico aeróbico traz benefícios para hipertensos. Objetivo: Verificar os efeitos do treinamento físico aeróbico sobre a contratilidade e a concentração intracelular de Ca2+ transitória em miócitos e a expressão do microRNA 214 no ventrículo esquerdo (VE) de ratos espontaneamente hipertensos (SHR). Métodos: SHR e ratos Wistar normotensos com 16 semanas de idade foram divididos em 4 grupos de 13 animais cada: hipertenso sedentário (HS); hipertenso treinado (HT); normotenso sedentário (NS); normotenso treinado (NT). Os animais dos grupos HT e NT foram submetidos a um programa de treinamento progressivo de corrida em esteira, 5 dias/semana, 1 hora/dia, em intensidade de 60-70% da velocidade máxima de corrida, durante 8 semanas. Adotou-se p ≤ 0,05 como nível de significância em todas as comparações. Resultados: O treinamento físico reduziu a pressão arterial sistólica nos animais hipertensos. Nos animais normotensos, o treinamento físico reduziu o tempo para 50% de relaxamento celular e o tempo para o pico de contração celular, mas aumentou o tempo para 50% de decaimento da concentração intracelular de Ca2+ transitória. Nos animais SHR, o treinamento físico aumentou a amplitude e reduziu o tempo para 50% de decaimento da concentração intracelular de Ca2+ transitória, sem alterar a contratilidade celular. O treinamento físico aumentou a expressão do miR-214 apenas nos animais hipertensos. Conclusão: O treinamento aeróbico utilizado aumenta a disponibilidade e acelera o sequestro de Ca2+ intracelular em miócitos do VE de ratos hipertensos, apesar do aumento da expressão de miR-214 e da manutenção da contratilidade celular.


Subject(s)
Animals , Rats , Physical Conditioning, Animal/physiology , Blood Pressure/physiology , Calcium/metabolism , Myocytes, Cardiac/metabolism , Hypertension/metabolism , Myocardial Contraction/physiology , Rats, Inbred SHR , Calcium Signaling , Myocytes, Cardiac/physiology , MicroRNAs/metabolism , Hypertension/physiopathology
8.
Rev. méd. Chile ; 146(6): 693-701, jun. 2018. tab, graf
Article in Spanish | LILACS | ID: biblio-961449

ABSTRACT

Background: There is a wide interindividual variability in the response to a period of exercise training. The science have reported that a minimum of participants could be non-responders for improving different health-related outcomes after training. Aim: To compare the effects of a 6-weeks exercise program on body composition, cardiovascular and metabolic outcomes patients with type 2 diabetes and hypertension. Material and Methods: Data from 23 trained subjects were used in a secondary analysis of the response to exercise. Of these, 14 were considered adherent to training and nine as non-adherent. Body mass, height, waist circumference, four skinfolds and their sum, blood pressure and plasma triglyceride levels were assessed before and after the training period. Results: Among adherent participants, significant reductions were observed in the sum of four skinfolds (30 ± 7 to 27 ± 6 mm, p ≤ 0.05), systolic blood pressure (133 ± 18 to 127 ± 20 mmHg; p ≤ 0.05) and plasma triglycerides (125 ± 58 to 102 ± 34 mg/dL; p ≤ 0.05). No changes were observed in weight or diastolic blood pressure. Among non-adherent participants, no changes of measured parameters were observed. Among adherent participants, 57% were considered as non-responders for waist circumference, 7% for the sum of skinfold thickness, 50% for systolic blood pressure, 64% for diastolic blood pressure and 57% for plasma triglycerides. Conclusions: Participants with a good adherence to a 6-weeks exercise training program experienced overall improvement in body composition, blood pressure and plasma triglycerides. The prevalence of non-responders varied considerably among measured outcomes.


Subject(s)
Humans , Male , Female , Diabetes Mellitus, Type 2/metabolism , Diabetes Mellitus, Type 2/prevention & control , Exercise Therapy/methods , High-Intensity Interval Training/methods , Hypertension/metabolism , Hypertension/prevention & control , Time Factors , Triglycerides/blood , Blood Pressure/physiology , Body Composition/physiology , Anthropometry , Reproducibility of Results , Risk Factors , Patient Compliance , Treatment Outcome , Statistics, Nonparametric
9.
Arq. bras. cardiol ; 110(6): 558-567, June 2018. tab, graf
Article in English | LILACS | ID: biblio-950175

ABSTRACT

Abstract Background: Obesity leads to a chronic inflammatory state, endothelial dysfunction and hypertension. Objective: To establish the time-course of events regarding inflammatory markers, endothelial dysfunction, systolic blood pressure (SBP) in obesity in only one experimental model. Methods: We fed male Wistar rats (eight-week age) with a standard diet (Control - CT, n = 35), or palatable high-fat diet (HFD, n = 35) for 24 weeks. Every six weeks, 7 animals from each group were randomly selected for euthanasia. SBP and serum levels of interleukin-6, tumor necrosis factor-α, C-reactive protein, adiponectin and nitric oxide were determined. Endothelial and vascular smooth muscle functions were determined in dissected aorta and lipid peroxidation was measured. Statistical significance was set at p < 0.05. Results: Levels of pro-inflammatory cytokines began to increase after six weeks of a high-fat diet, while those of the anti-inflammatory cytokine adiponectin decreased. Interestingly, the endothelial function and serum nitric oxide began to decrease after six weeks in HFD group. The SBP and lipid peroxidation began to increase at 12 weeks in HFD group. In addition, we showed that total visceral fat mass was negatively correlated with endothelial function and positively correlated with SBP. Conclusion: Our results show the time-course of deleterious effects and their correlation with obesity.


Resumo Fundamento: A obesidade leva a um estado de inflamação crônica, disfunção endotelial e hipertensão. Objetivo: Estabelecer a sequência de eventos relacionados a marcadores inflamatórios, disfunção endotelial e pressão arterial sistólica (PAS) na obesidade em um modelo experimental. Métodos: Ratos Wistar machos (8 semanas de idade) receberam dieta padrão (Controle - CT, n = 35) ou uma dieta palatável hiperlipídica (DHL, n = 35) por 24 semanas. A cada seis semanas, 7 animais de cada grupo foram aleatoriamente selecionados para eutanásia. Foram determinados a PAS, e níveis séricos de interleucina-6, fator de necrose tumoral-a, proteína C reativa, adiponectina e óxido nítrico. As funções do músculo liso endotelial e vascular foram determinadas na aorta dissecada, e medida a peroxidação lipídica. A significância estatística foi estabelecida em p < 0,05. Resultados: os níveis das citocinas pró-inflamatórias começaram a aumentar após seis semanas de dieta hiperlipídica, enquanto os níveis da citocina anti-inflamatória adiponectina diminuíram. Um resultado interessante foi a redução da função endotelial e do óxido nítrico após seis semanas no grupo DHL. Além disso, mostramos que a massa de tecido adiposo visceral total esteve negativamente correlacionada com função endotelial e positivamente correlacionada com a PAS. Conclusão: Nossos resultados demonstram a progressão temporal dos efeitos deletérios e sua correlação com a obesidade.


Subject(s)
Animals , Male , Endothelium, Vascular/physiopathology , Diet, High-Fat/adverse effects , Hypertension/physiopathology , Inflammation/physiopathology , Obesity/physiopathology , Time Factors , Blood Pressure/physiology , Enzyme-Linked Immunosorbent Assay , Endothelium, Vascular/metabolism , Lipid Peroxidation , Random Allocation , Cytokines/analysis , Rats, Wistar , Disease Models, Animal , Intra-Abdominal Fat , Hypertension/metabolism , Inflammation/metabolism , Nitric Oxide/blood , Obesity/complications , Obesity/metabolism
10.
Braz. dent. j ; 29(3): 309-315, May-June 2018. tab, graf
Article in English | LILACS | ID: biblio-951550

ABSTRACT

Abstract The aim of this study was to investigate salivary levels of TGFβ1 and proliferation/ maturation of epithelial mucosa cells in diabetic and hypertensive patients. Design: in this cross-sectional study, whole stimulated saliva and oral mucosa exfoliative cytology specimens were collected from 39 patients that were healthy (control, n=10) or presented history of arterial hypertension (HAS, n=9), diabetes mellitus (DM, n=10) or both (DM+HAS, n=10). Salivary flow rate (SFR), TGFβ1 level in saliva, AgNORs and the epithelial maturation were evaluated. Non-parametric Kruskal-Wallis test, followed by Dunn's multiple comparison post-test and the Spearman test correlation analysis were used. SFR showed a significant decreased in DM and DM+HAS (0.47±0.11 and 0.64±0.43 mL/min) when compared to control (1.4±0.38 mL/min). DM+HAS presented the highest value of TGFβ1 concentration (24.72±5.89 pg/mL). It was observed a positive correlation between TGFβ1 and glycaemia (R=0.6371; p<0.001) and a negative correlation between TGFβ1 and saliva (R=-0.6162; p<0.001) and glycaemia and SFR (R=-0.5654; P=0.001). AgNORs number and status of maturation of mucosa cells were similar for all conditions. DM and DM+HAS presented the lowest SFR, which correlated with increased TGFβ1 levels. Despite the higher TGFβ1 secretion it was not observed changes in the morphology or proliferation of epithelial cells when diabetes or hypertension was present.


Resumo O objetivo deste estudo foi investigar os níveis de TGFβ1 na saliva e a proliferação/maturação das células epiteliais da mucosa em paciente diabéticos e hipertensos. Neste estudo transversal, saliva estimulada e amostras de citologia exfoliativa de mucosa oral foram coletadas de um total de 39 pacientes que se apresentavam saudáveis (controle, n=10) ou com história de hipertensão arterial (HAS, n=9), diabetes mellitus (DM, n=10) ou ambos (DM+HAS, n=10). Taxa de fluxo salivar (SFR), níveis de TGFβ1 na saliva, AgNORs e maturação epitelial foram avaliados. Teste não-paramétrico de Kruskal-Wallis, seguido de comparação múltipla de Dunn e correlação de Spearman foram utilizados para as análises. SFR diminuiu significantemente em DM e DM+HAS (0,47±0,11 e 0,64±0,43 mL/min) quando comparado ao controle (1,4±0,38 mL/min). DM+HAS apresentou os maiores valores de concentração de TGFβ1 (24,72±5,89 pg/mL). Foi observada uma correlação positiva entre TGFβ1 e glicemia (R=0,6371; p<0,001) e uma correlação negativa entre TGFβ1 e saliva (R=-0,6162; p<0,001) e glicemia e SFR (R=-0,5654; p=0,001). Número de AgNORs e o padrão da maturação das células epiteliais foram similares entre os todos grupos. DM e DM+HAS apresentaram os menores valores de SFR, os quais foram correlacionados com o aumento nos níveis de TGFβ1. Apesar da maior secreção de TGFβ1, não foram observadas mudanças na morfologia ou proliferação das células epiteliais quando o paciente apresentava diabetes ou hipertensão.


Subject(s)
Humans , Male , Female , Adult , Middle Aged , Saliva/metabolism , Diabetes Mellitus/metabolism , Transforming Growth Factor beta1/metabolism , Hypertension/metabolism , Mouth Mucosa/metabolism , Mouth Mucosa/pathology , Salivation , Secretory Rate , Blood Glucose/metabolism , Case-Control Studies , Cross-Sectional Studies , Antigens, Nuclear , Diabetes Mellitus/pathology , Diabetes Mellitus/blood , Hypertension/pathology
11.
Arq. bras. cardiol ; 108(3): 228-236, Mar. 2017. tab, graf
Article in English | LILACS | ID: biblio-838702

ABSTRACT

Abstract Background: Physical exercise is an important tool for the improvement of endothelial function. Objective: To assess the effects of acute dynamic resistance exercise on the endothelial function of spontaneously hypertensive rats (SHR). Methods: Ten minutes after exercise, the aorta was removed to evaluate the expression of endothelial nitric oxide synthase (eNOS), phosphorylated endothelial nitric oxide synthase (p-eNOS1177) and inducible nitric oxide synthase (iNOS) and to generate concentration-response curves to acetylcholine (ACh) and to phenylephrine (PHE). The PHE protocol was also performed with damaged endothelium and before and after NG-nitro-L-arginine methyl ester (L-NAME) and indomethacin administration. The maximal response (Emax) and the sensitivity (EC50) to these drugs were evaluated. Results: ACh-induced relaxation increased in the aortic rings of exercised (Ex) rats (Emax= -80 ± 4.6%, p < 0.05) when compared to those of controls (Ct) (Emax = -50 ± 6.8%). The Emax to PHE was decreased following exercise conditions (95 ± 7.9%, p < 0.05) when compared to control conditions (120 ± 4.2%). This response was abolished after L-NAME administration or endothelial damage. In the presence of indomethacin, the aortic rings' reactivity to PHE was decreased in both groups (EC50= Ex -5.9 ± 0.14 vs. Ct -6.6 ± 0.33 log µM, p < 0.05 / Emax = Ex 9.5 ± 2.9 vs. Ct 17 ± 6.2%, p < 0.05). Exercise did not alter the expression of eNOS and iNOS, but increased the level of p-eNOS. Conclusion: A single resistance exercise session improves endothelial function in hypertensive rats. This response seems to be mediated by increased NO production through eNOS activation.


Resumo Fundamento: O exercício físico é uma importante ferramenta para o aprimoramento da função endotelial. Objetivo: Avaliar os efeitos do exercício dinâmico resistido agudo na função endotelial de ratos espontaneamente hipertensos (SHR). Métodos: Após 10 minutos de exercício, a aorta foi removida para avaliação da expressão de óxido nítrico sintase endotelial (eNOS), óxido nítrico sintase endotelial fosforilada (p-eNOS1177) e óxido nítrico sintase endotelial induzível (iNOS), e para a construção de curvas concentração-resposta de acetilcolina (ACT) e fenilefrina (FEN). O protocolo FEN foi também realizado com lesão endotelial e antes e depois da administração de N-nitro-L-arginina metil éster (L-NAME) e indometacina. A resposta máxima (Emax) e a sensibilidade (EC50) a esses fármacos foram avaliadas. Resultados: Houve aumento do relaxamento induzido por ACT nos anéis aórticos dos ratos exercitados (Ex) (Emax = -80 ± 4,6%; p < 0,05) quando comparado àquele dos controles (Ct) (Emax = -50 ± 6,8%). A Emax à FEN diminuiu após exercício (95 ± 7,9%; p < 0,05) quando comparada àquela dos controles (120 ± 4,2%). Tal resposta foi abolida após administração de L-NAME ou lesão endotelial. Na presença de indometacina, a reatividade dos anéis aórticos à FEN diminuiu nos dois grupos (EC50= Ex -5,9 ± 0,14 vs. Ct -6,6 ± 0,33 log µM; p < 0,05/ Emax = Ex 9,5 ± 2,9 vs. Ct 17 ± 6,2%; p < 0,05). O exercício não alterou a expressão de eNOS e de iNOS, mas aumentou o nível de p-eNOS. Conclusão: Uma única sessão de exercício resistido melhora a função endotelial em ratos hipertensos. Essa resposta parece ser mediada por elevação da produção de NO através de ativação de eNOS.


Subject(s)
Animals , Male , Aorta, Thoracic/physiopathology , Aorta, Thoracic/metabolism , Physical Conditioning, Animal/physiology , Endothelium, Vascular/physiopathology , Endothelium, Vascular/metabolism , Aorta, Thoracic/chemistry , Phenylephrine , Phosphorylation/physiology , Time Factors , Vasoconstriction/physiology , Endothelium, Vascular/chemistry , Acetylcholine , Prostaglandins/metabolism , Blotting, Western , NG-Nitroarginine Methyl Ester , Nitric Oxide Synthase Type II/metabolism , Nitric Oxide Synthase Type III/analysis , Nitric Oxide Synthase Type III/metabolism , Exercise Test , Hypertension/physiopathology , Hypertension/metabolism , Nitric Oxide/analysis , Nitric Oxide/metabolism
12.
Arq. bras. cardiol ; 108(2): 116-121, Feb. 2017. tab, graf
Article in English | LILACS | ID: biblio-838695

ABSTRACT

Abstract Background: Despite knowing that resveratrol has effects on blood vessels, blood pressure and that phytostrogens can also improve the endothelium-dependent relaxation/vasodilation, there are no reports of reveratrol's direct effect on the endothelial function and blood pressure of animals with estrogen deficit (mimicking post-menopausal increased blood pressure). Objective: To verify the effect of two different periods of preventive treatment with resveratrol on blood pressure and endothelial function in ovariectomized young adult rats. Methods: 3-month old female Wistar rats were used and distributed in 6 groups: intact groups with 60 or 90 days, ovariectomized groups with 60 or 90 days, and ovariectomized treated with resveratrol (10 mg/kg of body weight per day) for 60 or 90 days. The number of days in each group corresponds to the duration of the experimental period. Vascular reactivity study was performed in abdominal aortic rings, systolic blood pressure was measured and serum nitric oxide (NO) concentration was quantified. Results: Ovariectomy induced blood pressure increase 60 and 90 days after surgery, whereas the endothelial function decreased only 90 days after surgery, with no difference in NO concentration among the groups. Only longer treatment (90 days) with resveratrol was able to improve the endothelial function and normalize blood pressure. Conclusion: Our results suggest that 90 days of treatment with resveratrol is able to improve the endothelial function and decrease blood pressure in ovariectomized rats.


Resumo Fundamentos: Apesar de se saber que o resveratrol apresenta efeitos sobre a pressão arterial e os vasos sanguíneos, e que os fitoestrógenos podem melhorar o relaxamento/vasodilatação dependente do endotélio, não há relatos do efeito direto do resveratrol sobre a pressão arterial e a função endotelial em animais com deficiência de estrógeno (mimetizando a pressão arterial aumentada pós-menopausa). Objetivo: Verificar o efeito de dois diferentes períodos de tratamento preventivo com resveratrol sobre a pressão arterial e a função endotelial em ratas adultas jovens ovariectomizadas. Métodos: Foram utilizadas ratas Wistar com 3 meses de idade, distribuídas em 6 grupos: grupos intactas com 60 ou 90 dias, grupos ovariectomizadas com 60 ou 90 dias, grupos ovariectomizadas e tratadas com resveratrol na dose de 10mg/kg de massa corporal por dia, durante 60 ou 90 dias, sendo o número de dias em cada grupo relativo à duração do período experimental. Foi realizado um estudo de reatividade vascular em anéis da aorta abdominal, mensurada a pressão arterial sistólica e quantificada a concentração sérica de óxido nítrico (NO). Resultados: A ovariectomia induziu aumento da pressão arterial 60 e 90 dias após a cirurgia, enquanto a função endotelial decaiu apenas após 90 dias, e não houve diferença na concentração de NO entre os grupos. Apenas o tratamento prolongado com resveratrol (90 dias) foi capaz de melhorar a função endotelial e normalizar a pressão arterial. Conclusão: Nossos resultados sugerem que o tratamento por 90 dias com resveratrol é capaz de melhorar a função endotelial e diminuir a pressão sanguínea em ratas ovariectomizadas.


Subject(s)
Animals , Female , Stilbenes/pharmacology , Blood Pressure/drug effects , Endothelium, Vascular/drug effects , Ovariectomy , Antioxidants/pharmacology , Reference Values , Stilbenes/therapeutic use , Time Factors , Blood Pressure/physiology , Endothelium, Vascular/physiology , Reproducibility of Results , Treatment Outcome , Rats, Wistar , Estrogens/deficiency , Resveratrol , Hypertension/metabolism , Hypertension/drug therapy , Nitrates/blood , Nitric Oxide/blood , Antioxidants/therapeutic use
13.
Säo Paulo med. j ; 133(2): 73-77, Mar-Apr/2015. tab
Article in English | LILACS | ID: lil-746644

ABSTRACT

CONTEXT AND OBJECTIVE: Several studies have evaluated the role of low 25-hydroxyvitamin D (25OHD3) in the pathogenesis of type 2 diabetes (T2DM) and have presented controversial results. The metabolic processes that culminate in T2DM begin under prediabetic conditions. Our aim was to analyze the association between 25OHD3 and glucose metabolism in individuals who were free from but at elevated risk of diabetes. DESIGN AND SETTING: Cross-sectional study at a tertiary hospital. METHODS: Anthropometric and laboratory profiles were determined in patients with one or more of the following risk factors: hypertension; body mass index (BMI) ≥ 25 kg/m2; waist circumference > 80 cm for women and > 94 cm for men; first-degree relatives with diabetes; women with large-for-gestational-age newborns or with gestational T2DM; HDL-cholesterol (high density lipoprotein) < 35 mg/dl; and triglycerides > 250 mg/dl. The patients were divided into two groups: one with prediabetes (abnormal fasting plasma glucose or oral glucose tolerance test) and the other with normal glucose (euglycemic). RESULTS: There was no statistically significant difference between the prediabetic group (n = 38) and euglycemic group (n = 15) regarding age (66.4 ± 10.6 versus 62.6 ± 9.1 years), gender (52.6 versus 73.3% female) and BMI (30.1 ± 4.61 versus 27.9 ± 4.7 kg/m2). Low serum levels of 25OHD3 were found in both groups, without any statistically significant difference between them (29.1 ± 11.8 versus 26.87 ± 9.2 ng/dl). CONCLUSION: There was no association between 25OHD3 levels and the clinical or laboratorial variables analyzed. .


CONTEXTO E OBJETIVO: Vários estudos já avaliaram o papel da 25-hidroxivitamina D (25OHD3) na patogênese do diabetes tipo 2 (DM2) e apresentaram resultados controversos. Os processos metabólicos que culminam no DM2 se iniciam no pré-diabetes. Nosso objetivo foi analisar a associação da 25OHD3 com o metabolismo glicêmico em indivíduos sem diagnóstico mas com alto risco para diabetes. TIPO DE ESTUDO E LOCAL: Estudo transversal em hospital terciário. MÉTODOS: Medidas antropométricas e laboratoriais foram determinadas em pacientes com um ou mais dos fatores de risco: hipertensão; índice de massa corpórea (IMC) ≥ 25 kg/m2; circunferência abdominal > 80 cm no sexo feminino e > 94 cm no sexo masculino; parentes de primeiro grau com diabetes; mulheres com filho nascido grande para idade gestacional ou com DM2 na gravidez; colesterol HDL (high density lipoprotein) < 35 mg/dl e triglicerídeo > 250 mg/dl. Os pacientes foram divididos em dois grupos: um com pré-diabetes (glicemia de jejum ou teste de tolerância oral à glicose alterados) e outro com glicose normal (euglicêmicos). RESULTADOS: Entre pré-diabéticos (n = 38) e euglicêmicos (n = 15) não houve diferença estatística na idade (66,4 ± 10,6 versus 62,6 ± 9,1 anos), gênero (52,6 versus 73,3% feminino) e IMC (30,1 ± 4,61 versus 27,9 ± 4,7 kg/m2). Baixos niveis séricos de 25OHD3 foram encontrados nos dois grupos, sem diferença estatística entre eles (29,1 ± 11,8 versus 26,87 ± 9,2 ng/dl). CONCLUSÃO: Não houve associação entre os níveis de 25OHD3 e as variáveis clínicas e laboratoriais analisadas. .


Subject(s)
Aged , Female , Humans , Male , Middle Aged , /metabolism , Hypertension/metabolism , Prediabetic State/metabolism , Vitamin D/analogs & derivatives , Body Mass Index , Brazil , Blood Glucose/analysis , Cross-Sectional Studies , Cholesterol/blood , Dyslipidemias/metabolism , Glucose Tolerance Test , Luminescent Measurements , Risk Factors , Tertiary Care Centers , Triglycerides/blood , Vitamin D/metabolism , Waist Circumference/physiology
14.
Int. arch. otorhinolaryngol. (Impr.) ; 19(1): 1-4, Jan-Mar/2015. tab, graf
Article in English | LILACS | ID: lil-741543

ABSTRACT

Introduction Otosclerosis is a disease that causes bone resorption and deposition in the auditory structures, leading to deafness. Many studies have evaluated the histopathology of the stapes footplate in this disease (osteoblasts, osteoclasts, vascular proliferation, fibroblasts, and histiocytes), but we found no studies in the literature involving the histology of the superstructure of the stapes. Objectives To perform an analysis under optical microscopy of histopathologic findings of the superstructure of the stapes from patients with otosclerosis. Methods A contemporary cross-sectional cohort study of pathology analysis of superstructures of the stapes of patients with otosclerosis. Results Fifteen superstructures of stapes in patients with otosclerosis operated in our service and four stapes of cadavers used for dissection (controls) were evaluated. No areas of bone resorption or deposition or presence of osteoclasts and osteoblasts in the superstructure of the stapes were found. However, we found in themore distal portions of the crura areas with prominent cementitious lines and woven bone, which was different than the mature trabecular bone found in the head of the stapes or in the controls. Conclusion There were histologic changes in the superstructure of the stapes in patients with otosclerosis operated in our service. .


Subject(s)
Animals , Humans , Glucocorticoids/metabolism , Hypertension/metabolism , Kidney/physiology , Sodium/metabolism , Ion Transport , Kidney/metabolism , Renin-Angiotensin System , Water-Electrolyte Balance
15.
Rio de Janeiro; s.n; 2015. 102 f p.
Thesis in Portuguese | LILACS | ID: lil-756705

ABSTRACT

Em pacientes hipertensos e diabéticos, o sistema renina-angiotensina-aldosterona está relacionado com disfunção endotelial, rigidez vascular e aterosclerose. As principais medicações disponíveis para a inibição desse sistema são os inibidores da enzima conversora de angiotensina e os bloqueadores do receptor AT1 de angiotensina. A maioria das diretrizes internacionais faz as mesmas recomendações para as duas classes, mas diferenças no seu mecanismo de ação podem ter relevância clínica. O objetivo principal foi comparar benazepril e losartana em pacientes hipertensos e diabéticos com pressão arterial não controlada por anlodipino, analisando parâmetros inflamatórios (proteína C reativa), da função endotelial (através da dilatação mediada por fluxo da artéria braquial) e de rigidez vascular (através da velocidade da onda de pulso e das pressões aórticas). O objetivo secundário foi, através de uma análise post-hoc, pesquisar se há interação entre as estatinas e os inibidores do sistema renina-angiotensina-aldosterona. Pressão arterial, função endotelial e rigidez vascular foram comparados entre usuários e não-usuários de estatina. Os dados estão apresentados como mediana (intervalo interquartil). Os resultados principais mostraram que o grupo benazepril apresentou menor proteína C reativa [0,38 (0,15-0,95) mg/dl vs 0,42 (0,26-0,59) mg/dl, p=0,020]. Houve, ainda, uma leve melhora da dilatação mediada por fluxo da artéria braquial no grupo benazepril (aumento 45%, p=0,057) em comparação com o grupo losartana (aumento 19%, p=0,132). Não houve diferença na velocidade da onda de pulso [8,5 (7,8-9,4) m/s vs 8,5 (7,0-9,7) m/s, p=0,280] e na pressão aórtica sistólica [129 (121-145) mmHg vs 123 (117-130) mmHg, p=0,934] entre os grupos benazepril e losartana...


In hypertensive diabetic patients, the renin-angiotensin-aldosterone system is related to endothelial dysfunction, vascular stiffness and atherosclerosis. Angiotensin converting enzyme inhibitors and angiotensin receptor blockers are two of the most important medications that inhibit this system. Most international guidelines recommend them interchangeably, albeit small differences may have clinical relevance. The main objective was to compare inflammatory parameters (by C-reactive protein), endothelial function (by flow-mediated vasodilation) and vascular stiffness (by pulse wave velocity and aortic pressures) between benazepril and losartan in hypertensive diabetic patients whose blood pressure was not controlled by amlodipine. The secondary objective was a post-hoc analysis to study possible synergism between statins and renin-angiotensin-aldosterone system inhibitors. Blood pressure reduction, endothelial function and vascular stiffness were compared between patients using or not statins. Main results showed that C-reactive protein had lower values in benazepril group [0.38 (0.15-0.95) mg/dl vs 0.42 (0.26-0.59) mg/dl, p=0.020]. There was a slightly higher flow-mediated vasodilation response in benazepril group (45% of increase, p=0.057) than in losartan group (19% of increase, p=0.132). Aortic systolic blood pressure [129 (121-145) mmHg vs 123 (117-130) mmHg, p=0.934] and carotid-femoral pulse wave velocity [8.5 (7.8-9.4) m/s vs 8.5 (7.0-9.7) m/s, p=0.280] were the same between groups. Secondary results showed that patients using statins had greater reduction in mean systolic blood pressure in 24 hour monitoring [134 (120-146) mmHg to 122 (114-135) mmHg, p=0.007] than patients not using statins [137 (122-149) mmHg to 128 (122-140) mmHg, p=0.362]. Patients using statins had higher flow-mediated vasodilation response [6.5% (5.1-7.1) to 10.9% (7.3-12.2), p=0.003] than those not using statins [7.5% (6.0-10.2) to 8.3% (7.5-9.9), p=0.820]...


Subject(s)
Humans , Male , Female , Diabetes Mellitus/metabolism , Diabetes Mellitus/drug therapy , Endothelium, Vascular , Hypertension/metabolism , Hypertension/drug therapy , Vascular Stiffness , Amlodipine/administration & dosage , Antihypertensive Agents/administration & dosage , Antihypertensive Agents/analysis , Cardiovascular Diseases , Diabetes Mellitus/physiopathology , Diabetes Mellitus/prevention & control , Hypertension/physiopathology , Hypertension/prevention & control , Renin-Angiotensin System
16.
Braz. j. med. biol. res ; 47(11): 960-965, 11/2014. tab, graf
Article in English | LILACS | ID: lil-723901

ABSTRACT

In cardiomyocytes, calcium (Ca2+) release units comprise clusters of intracellular Ca2+ release channels located on the sarcoplasmic reticulum, and hypertension is well established as a cause of defects in calcium release unit function. Our objective was to determine whether endurance exercise training could attenuate the deleterious effects of hypertension on calcium release unit components and Ca2+ sparks in left ventricular myocytes of spontaneously hypertensive rats. Male Wistar and spontaneously hypertensive rats (4 months of age) were divided into 4 groups: normotensive (NC) and hypertensive control (HC), and normotensive (NT) and hypertensive trained (HT) animals (7 rats per group). NC and HC rats were submitted to a low-intensity treadmill running protocol (5 days/week, 1 h/day, 0% grade, and 50-60% of maximal running speed) for 8 weeks. Gene expression of the ryanodine receptor type 2 (RyR2) and FK506 binding protein (FKBP12.6) increased (270%) and decreased (88%), respectively, in HC compared to NC rats. Endurance exercise training reversed these changes by reducing RyR2 (230%) and normalizing FKBP12.6 gene expression (112%). Hypertension also increased the frequency of Ca2+ sparks (HC=7.61±0.26 vs NC=4.79±0.19 per 100 µm/s) and decreased its amplitude (HC=0.260±0.08 vs NC=0.324±0.10 ΔF/F0), full width at half-maximum amplitude (HC=1.05±0.08 vs NC=1.26±0.01 µm), total duration (HC=11.51±0.12 vs NC=14.97±0.24 ms), time to peak (HC=4.84±0.06 vs NC=6.31±0.14 ms), and time constant of decay (HC=8.68±0.12 vs NC=10.21±0.22 ms). These changes were partially reversed in HT rats (frequency of Ca2+ sparks=6.26±0.19 µm/s, amplitude=0.282±0.10 ΔF/F0, full width at half-maximum amplitude=1.14±0.01 µm, total duration=13.34±0.17 ms, time to peak=5.43±0.08 ms, and time constant of decay=9.43±0.15 ms). Endurance exercise training attenuated the deleterious effects of hypertension on calcium release units of left ventricular myocytes.


Subject(s)
Animals , Male , Calcium/physiology , Heart Ventricles/metabolism , Hypertension/therapy , Motor Activity/physiology , Myocytes, Cardiac/metabolism , Physical Conditioning, Animal/methods , Calcium Signaling/physiology , Exercise Test/methods , Heart Ventricles/cytology , Hypertension/metabolism , Rats, Inbred SHR , Rats, Wistar , Ryanodine Receptor Calcium Release Channel/genetics , Ryanodine Receptor Calcium Release Channel/metabolism , Tacrolimus Binding Proteins/genetics , Tacrolimus Binding Proteins/metabolism
17.
Int. j. morphol ; 32(3): 839-843, Sept. 2014. ilus
Article in English | LILACS | ID: lil-728276

ABSTRACT

Metformin, an oral biguanide approved for the treatment of type II diabetes is widely prescribed for other clinical conditions. Currently, metformin is being investigated as potential anti-tumor agent. However, there have been recent concerns about hepatotoxicity associated with the use of metformin. This study, by means of high resolution transmission electron microscopy (TEM) and morphometry, investigated potential ultrastructural changes induced by metformin treatment on the hepatocytes of spontaneously hypertensive rats (SHR). Morphometric analysis was carried out on images of randomly selected cells from sectioned gluteraldehyde-osmium-fixed, Epon embedded liver tissue. One-way analysis of variance (ANOVA) on morphometric data showed statistically significant differences in the mean volume density (MVD) of lipid bodies (F=136.48, P<0.0001)and mean surface density (MSD) of endoplasmic reticulum (ER) (F=12.45, P<0.003) between hepatocytes of control (n=8) and metformin-treated (MT) (n=8) animals. MVD for control group was 5.42% (±0.36 SEM) but decreased significantly in the MT group (1.13%, ±0.04 SEM). Similarly, MSD of ER for control was 24.7 µm2/µm3 (±1.64 SEM) but decreased for MT animals (18.90 µm2/µm3, ±0.28 SEM). These data are most likely consistent with the effects of metformin on lipid metabolism, and may not reflect on hepatotoxicity induced by the drug, in SHRs.


La metformina, una biguanida oral aprobada para el tratamiento de la diabetes tipo II, es también ampliamente prescrita para otros cuadros clínicos. Actualmente, la metformina está siendo investigada como posible agente anti-tumoral. Sin embargo, ha habido recientes preocupaciones acerca de la hepatotoxicidad asociada con el uso de metformina. En este estudio, por medio de la microscopía electrónica de transmisión (MET) de alta resolución y morfometría, se investigaron los posibles cambios ultraestructurales, inducidos por el tratamiento con metformina, en los hepatocitos de ratas espontáneamente hipertensas (REH). El análisis morfométrico se llevó a cabo en imágenes de células seleccionadas al azar a partir de tejido hepático seccionado, fijado con glutaraldehído-osmio e inmerso en Epon. El análisis de la varianza (ANOVA) de los datos morfométricos mostró diferencias significativas en la densidad de volumen medio (DVM) de cuerpos lipídicos (F=136,48, P<0,0001) y la densidad de superficie media (DSM) del retículo endoplasmático (RE) (F=12,45, P<0,003) entre los hepatocitos control (n=8) y los animales tratados con metformina (MT) (n=8). La DVM para el grupo control fue de 5,42% (±0,36 EEM), pero disminuyó significativamente en el grupo MT (1,13%, ±0,04 EEM). Del mismo modo, la DSM del RE para el grupo control fue de 24,7 µm2/µm3 (±1,64 EEM), pero disminuyó para los animales MT (18,90 µm2/µm3, ±0,28 EEM). Estos datos están probablemente más relacionados con los efectos de la metformina sobre el metabolismo de los lípidos, y no se relacionarían con la hepatotoxicidad por inducción de la droga, en REH.


Subject(s)
Animals , Rats , Hepatocytes/drug effects , Hypertension/metabolism , Metformin/administration & dosage , Analysis of Variance , Hepatocytes/ultrastructure , Microscopy, Electron, Transmission , Endoplasmic Reticulum/drug effects , Lipids/analysis , Metformin/pharmacology
18.
J. bras. nefrol ; 36(3): 271-279, Jul-Sep/2014. tab, graf
Article in Portuguese | LILACS | ID: lil-725507

ABSTRACT

Introdução: Ainda é controverso se ocorre sinergismo entre as diferentes medidas não farmacológicas utilizadas no tratamento da hipertensão arterial. Objetivo: Avaliar o efeito do exercício físico aeróbico, da sobrecarga oral de potássio e da sua associação sobre a pressão arterial, metabolismo glicídico, excreção urinária de albumina e morfologia glomerular de ratos espontaneamente hipertensos (SHR). Métodos: SHRs foram divididos em: Grupo Controle (SHR; dieta padrão e sedentário, n = 10); Grupo Exercício (SHR + E; treinado em esteira rolante, dieta padrão, n = 10), Grupo Potássio (SHR + K; sedentário, dieta rica em potássio, n = 10) e Grupo Exercício + Potássio (SHR + E + K; exercitado, dieta rica em potássio, n = 10). Semanalmente, foi aferido o peso corporal (PC) e a pressão arterial de cauda (PAC). Ao final de 16 semanas, foi realizado o Teste de Tolerância oral a Glicose. A albuminúria foi determinada nos períodos basal, na 8ª e 16ª semana. Após o sacrifício, foi realizada a análise do índice de esclerose glomerular e a pesagem da gordura visceral. Resultados: A PAC e o PC não variaram significativamente. Houve melhora da sensibilidade à insulina no Grupo Exercício e Grupo Potássio, mas não no Grupo Exercício + Potássio. Na 16ª semana, a albuminúria de todos os grupos foi significativamente menor que o grupo SHR Controle. O índice de esclerose glomerular e o peso da gordura visceral também foram significativamente menores em todos os grupos tratados quando comparados ao controle. Conclusão: A dieta rica em potássio e o exercício físico determinaram melhora no metabolismo glicídico, na albuminúria e na morfologia glomerular, porém, a sobreposição ...


Introduction: It is still controversial whether there are synergistic effects among different non-pharmacological interventions used in the treatment of hypertension. Objetives: To evaluate the effect of aerobic exercise, oral supplementation of potassium and their combination on blood pressure, glucose metabolism, urinary albumin excretion and glomerular morphology in spontaneously hypertensive rats (SHR). Methods: SHR were divided into groups: Control Group (SHR; standard diet and sedentary, n = 10), Exercise Group (SHR + E; trained on a treadmill, standard diet, n = 10), Potassium Group (SHR + K; sedentary, potassium supplementation, n = 10) and Group Exercise + Potassium (SHR + E + K, exercise, potassium supplementation n = 10). Weekly, body weight (BW) and tail blood pressure (TAP) were measured. At the end of 16 weeks, a Oral Glucose Tolerance Test was performed. Albuminuria was determined in the baseline period, at 8th and at 16th week. After sacrifice, the analysis of glomerular sclerosis index and visceral fat weight was performed. Results: The TAP and BW did not change significantly. There was improvement in insulin sensitivity in SHR + E and SHR + K, but not in SHR + E + K. At week 16, albuminuria in all groups was significantly lower than the SHR control. The glomerular sclerosis index and visceral fat content were also significantly lower in all groups compared to control. Conclusion: An oral supplementation of potassium and exercise led to an improvement in glucose metabolism, in albuminuria and glomerular morphology, however, the overlap of the treatments did not show synergism. .


Subject(s)
Animals , Male , Rats , Albuminuria/metabolism , Albuminuria/physiopathology , Blood Pressure/physiology , Glucose/metabolism , Hypertension/metabolism , Hypertension/physiopathology , Physical Conditioning, Animal/physiology , Potassium/administration & dosage , Dietary Supplements , Rats, Inbred SHR
19.
Clinics ; 69(3): 179-184, 3/2014. tab
Article in English | LILACS | ID: lil-703600

ABSTRACT

OBJECTIVES: We aimed to investigate whether glucocorticoid receptor gene polymorphisms are associated with clinical and metabolic profiles in patients with polycystic ovary syndrome. Polycystic ovary syndrome is a complex endocrine disease that affects 5-8% of women and may be associated with metabolic syndrome, which is a risk factor for cardiovascular disease. Cortisol action and dysregulation account for metabolic syndrome development in the general population. As glucocorticoid receptor gene (NR3C1) polymorphisms regulate cortisol sensitivity, we hypothesized that variants of this gene may be involved in the adverse metabolic profiles of patients with polycystic ovary syndrome. METHOD: Clinical, metabolic and hormonal profiles were evaluated in 97 patients with polycystic ovary syndrome who were diagnosed according to the Rotterdam criteria. The alleles of the glucocorticoid gene were genotyped. Association analyses were performed using the appropriate statistical tests. RESULTS: Obesity and metabolic syndrome were observed in 42.3% and 26.8% of patients, respectively. Body mass index was positively correlated with blood pressure, triglyceride, LDL-c, total cholesterol, glucose and insulin levels as well as HOMA-IR values and inversely correlated with HDL-c and SHBG levels. The BclI and A3669G variants were found in 24.7% and 13.4% of alleles, respectively. BclI carriers presented a lower frequency of insulin resistance compared with wild-type subjects. CONCLUSION: The BclI variant is associated with a lower frequency of insulin resistance in women with polycystic ovary syndrome. Glucocorticoid gene polymorphism screening during treatment of the syndrome may be useful for identifying subgroups of at-risk patients who would benefit the most from personalized treatment. .


Subject(s)
Adult , Female , Humans , Young Adult , Polycystic Ovary Syndrome/genetics , Polycystic Ovary Syndrome/metabolism , Polymorphism, Genetic/genetics , Receptors, Glucocorticoid/genetics , Alleles , Body Mass Index , Cholesterol , Fluoroimmunoassay , Gene Frequency , Genes, bcl-1/genetics , Hypertension/genetics , Hypertension/metabolism , Insulin Resistance/genetics , Metabolic Syndrome/genetics , Metabolic Syndrome/metabolism , Obesity/genetics , Obesity/metabolism , Polymerase Chain Reaction , Risk Factors , Statistics, Nonparametric , Time Factors
20.
Arq. bras. cardiol ; 102(1): 60-69, 1/2014. tab, graf
Article in Portuguese | LILACS | ID: lil-704042

ABSTRACT

Fundamento: O impacto pressão arterial (PA) na adolescência sobre outros fatores de risco cardiovascular em adultos jovens é importante para a prevenção primária. Objetivo: Avaliar a PA, índices antropométricos, perfil metabólico e inflamatório de jovens estratificados pelo comportamento da sua PA obtida há 18 anos. Métodos: Avaliaram-se 116 indivíduos, sendo 63 homes, pertencentes ao estudo do Rio de Janeiro (seguimento 17,76 ± 1,63 anos) em dois momentos: A1 (12,40 ± 1,49 anos) e A2 (30,09 ± 2,01 anos). Os 116 indivíduos foram divididos em dois grupos: GN (n = 71), PA normal em A1; e GH (n = 45): PA anormal em A1. A PA, o peso, a altura e o índice de massa corporal (IMC) foram obtidos em A1 e A2. Em A2, acrescentaram-se a circunferência abdominal (CA) e variáveis laboratoriais, metabólicas e inflamatórias. Resultados: 1) Os grupos não diferiram quanto à idade e sexo; 2) Em A2, GH apresentou maiores médias de peso, IMC, PA, insulina, HOMA-IR (p < 0,001), leptina (p < 0,02), Apolipoproteína B100 e A1 (p < 0,02), relação Apolipoproteína B100 / Apolipoproteína A1 (p < 0,010), maiores prevalências de sobrepeso/obesidade (p < 0,001), da CA aumentada (p < 0,001) e de hipertensão arterial (p < 0,02); 3) Não houve diferença entre os grupos para as variáveis inflamatórias; 4) Houve correlação positiva da PA em A1 com a PA, o IMC, e com a insulina, a leptina e o HOMA-IR em A2 (p < 0,05). Conclusões: A PA na adolescência se associou a maiores valores de PA, variáveis antropométricas e metabólicas na fase adulta jovem, mas não a variáveis inflamatórias. .


Background: The impact of blood pressure (BP) during adolescence on other cardiovascular risk factors in young adults is important for the primary prevention. Objective: To evaluate BP, anthropometric indexes, metabolic and inflammatory profiles in young individuals stratified by their BP behavior recorded for 18 years. Methods: A total of 116 individuals, of whom 63 were males, from the Rio de Janeiro study (follow-up of 17.76 ± 1.63 years), were assessed at two moments: A1 (12.40 ± 1.49 years) and A2 (30.09 ± 2.01 years). The 116 individuals were divided into two groups: GN (n = 71), of participants with normal BP at A1; and GH (n = 45), of those with abnormal BP at A1. BP, weight, height and body mass index (BMI) were measured at A1 and A2. At A2, abdominal circumference (AC) and laboratory, metabolic and inflammatory variables were included. Results: 1) No difference was observed between the groups as regards age and gender; 2) At A2, GH showed higher mean weight, BMI, BP, insulin, HOMA-IR (p < 0.001), leptin (p < 0.02), apolipoprotein B100 and A1 (p < 0.02), apolipoprotein B100 / apolipoprotein A1 ratio (p < 0.010); and higher prevalences of overweight/obesity (p < 0.001), of increased AC (p < 0.001) and of hypertension (p < 0.02); 3) No difference was observed between the groups as regards the inflammatory variables; 4) There was a positive correlation of BP at A1 with BP, BMI, insulin, leptin and HOMA-IR at A2 (p < 0.05). Conclusion: BP in adolescence was associated with higher values of BP, and anthropometric and metabolic variables in young adulthood, but not with inflammatory variables. .


Subject(s)
Adolescent , Adult , Child , Female , Humans , Male , Young Adult , Anthropometry , Adipokines/blood , Blood Pressure/physiology , Age Factors , Apolipoproteins/blood , Brazil , Cardiovascular Diseases/etiology , Cardiovascular Diseases/metabolism , Follow-Up Studies , Hypertension/metabolism , Inflammation Mediators/blood , Metabolic Syndrome/blood , Reference Values , Risk Factors
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