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2.
Clin. biomed. res ; 37(4): 323-329, 2017. tab, graf
Article in English | LILACS | ID: biblio-876698

ABSTRACT

Introduction: Important changes in human dietary pattern occurred in recent decades. Increased intake of processed foods leads to obesity, which is related with the development of chronic diseases such as type 2 diabetes mellitus, hypertension, as well as cardiovascular and chronic kidney diseases. The prevalence of hypertension has also dramatically increased in recent years, and high sodium intake contributes to this scenario. In healthy individuals, kidneys are the primary end-organs that regulate sodium homeostasis. This study aims to evaluate renal function parameters and systolic blood pressure measurements in an animal model of obesity. Methods: Sixty-day-old male Wistar rats (n=30) were divided into two groups: standard (SD) and cafeteria diet (CD). Cafeteria diet was altered daily and was composed by crackers, wafers, sausages, chips, condensed milk, and soda. All animals had free access to water and chow and the experiment was carried out for 6 weeks. Weight gain, sodium and liquid intake control, systolic blood pressure measurements, and renal function parameters were evaluated. Results: Animals exposed to cafeteria diet had an increase of 18% in weight compared to the control group. Sodium intake was increased by cafeteria diet and time (F(1,28)=773.666, P=0.001 and F(5,28)=2.859, P=0.02, respectively) and by the interaction of both factors (F(6,28)=2.859, P=0.02). On liquid intake occurred only effect of cafeteria diet and time (F(1,28)=147.04, P=0.001 and F(5,28)=3.996, P=0.003, respectively). Cafeteria diet exposure also induced an increase on creatinine serum levels (P=0.002), however this effect was not observed on creatinine urine levels (P>0.05) nor on systolic pressure measurements (Students' t test, P>0.05). Conclusions: Obesity induced by cafeteria diet exposure increases liquid intake and alters creatinine serum levels, an important renal function marker. Considering the high consumption of hypercaloric food currently in the world, further studies are required to elucidate the modifications on renal function triggered by this diet over time (AU)


Subject(s)
Animals , Male , Rats , Creatinine/blood , Diet, Western/adverse effects , Drinking/drug effects , Hypertension/chemically induced , Kidney/physiopathology , Arterial Pressure/drug effects , Creatinine/urine , Disease Models, Animal , Kidney/drug effects , Obesity/blood , Obesity/etiology , Rats, Wistar , Sodium, Dietary/adverse effects
3.
Braz. j. med. biol. res ; 49(6): e5116, 2016. tab, graf
Article in English | LILACS | ID: biblio-951683

ABSTRACT

Supraphysiological administration of anabolic androgenic steroids has been linked to increased blood pressure. The widely distributed amino acid taurine seems to be an effective depressor agent in drug-induced hypertension. The purpose of this study was to assess the impact of chronic high dose administration of nandrolone decanoate (DECA) and taurine on blood pressure in rats and to verify the potentially involved mechanisms. The study was conducted in 4 groups of 8 adult male Wistar rats, aged 14 weeks, treated for 12 weeks with: DECA (A group); vehicle (C group); taurine (T group), or with both drugs (AT group). Systolic blood pressure (SBP) was measured at the beginning of the study (SBP1), 2 (SBP2) and 3 months (SBP3) later. Plasma angiotensin-converting enzyme (ACE) activity and plasma end products of nitric oxide metabolism (NOx) were also determined. SBP3 and SBP2 were significantly increased compared to SBP1 only in the A group (P<0.002 for both). SBP2, SBP3 and ACE activity showed a statistically significant increase in the A vs C (P<0.005), andvs AT groups (P<0.05), while NOx was significantly decreased in the A and AT groups vs controls (P=0.01). ACE activity was strongly correlated with SBP3 in the A group (r=0.71, P=0.04). These findings suggest that oral supplementation of taurine may prevent the increase in SBP induced by DECA, an effect potentially mediated by angiotensin-converting enzyme.


Subject(s)
Animals , Male , Blood Pressure/drug effects , Anabolic Agents/administration & dosage , Nandrolone/analogs & derivatives , Reference Values , Time Factors , Random Allocation , Anabolic Agents/adverse effects , Hypertension/chemically induced , Hypertension/prevention & control , Nandrolone/administration & dosage
4.
Clinics ; 70(11): 751-757, Nov. 2015. tab, graf
Article in English | LILACS | ID: lil-766151

ABSTRACT

OBJECTIVES: This study was conducted to determine whether the blood pressure-lowering effect of Nigella sativa might be mediated by its effects on nitric oxide, angiotensin-converting enzyme, heme oxygenase and oxidative stress markers. METHODS: Twenty-four adult male Sprague-Dawley rats were divided equally into 4 groups. One group served as the control (group 1), whereas the other three groups (groups 2-4) were administered L-NAME (25 mg/kg, intraperitoneally). Groups 3 and 4 were given oral nicardipine daily at a dose of 3 mg/kg and Nigella sativa oil at a dose of 2.5 mg/kg for 8 weeks, respectively, concomitantly with L-NAME administration. RESULTS: Nigella sativa oil prevented the increase in systolic blood pressure in the L-NAME-treated rats. The blood pressure reduction was associated with a reduction in cardiac lipid peroxidation product, NADPH oxidase, angiotensin-converting enzyme activity and plasma nitric oxide, as well as with an increase in heme oxygenase-1 activity in the heart. The effects of Nigella sativa on blood pressure, lipid peroxidation product, nicotinamide adenine dinucleotide phosphate oxidase and angiotensin-converting enzyme were similar to those of nicardipine. In contrast, L-NAME had opposite effects on lipid peroxidation, angiotensin-converting enzyme and NO. CONCLUSION: The antihypertensive effect of Nigella sativa oil appears to be mediated by a reduction in cardiac oxidative stress and angiotensin-converting enzyme activity, an increase in cardiac heme oxygenase-1 activity and a prevention of plasma nitric oxide loss. Thus, Nigella sativa oil might be beneficial for controlling hypertension.


Subject(s)
Animals , Male , Antihypertensive Agents/pharmacology , Blood Pressure/drug effects , Hypertension/drug therapy , Nigella sativa/chemistry , Plant Oils/pharmacology , Antihypertensive Agents/administration & dosage , Heme Oxygenase (Decyclizing)/metabolism , Hypertension/chemically induced , Models, Animal , Malondialdehyde/analysis , NADPH Oxidases/metabolism , NG-Nitroarginine Methyl Ester , Nicardipine/administration & dosage , Nicardipine/pharmacology , Nitric Oxide/blood , Oxidative Stress/drug effects , Peptidyl-Dipeptidase A/metabolism , Rats, Sprague-Dawley
5.
Säo Paulo med. j ; 133(3): 275-277, May-Jun/2015. tab, graf
Article in English | LILACS | ID: lil-752125

ABSTRACT

CONTEXT: Sunitinib is an antiangiogenic drug that has been approved for treating metastatic renal cancer. Its action as a tyrosine kinase inhibitor of vascular endothelial growth factor receptors (VEGFRs) and other angiogenesis receptors may lead to adverse effects such as hypertension and heart failure. However, reports in the literature on an association between sunitinib therapy and acute aortic dissection are rare. CASE REPORT: We report the case of a 68-year-old man with metastatic renal carcinoma who developed acute aortic dissection during sunitinib therapy. He had no history of hypertension or any other risk factor for aortic dissection. After aortic dissection had been diagnosed, sunitinib was withdrawn and an aortic endoprosthesis was placed. Afterwards, the patient was treated clinically with antihypertensive drugs and new therapy for renal cancer consisting of temsirolimus, an inhibitor of the mammalian target of rapamycin (mTOR) pathway. CONCLUSION: Hypertension is a common event when antiangiogenic drugs are used in oncology. However, knowledge of other severe cardiovascular events that may occur in these patients, such as acute aortic dissection, is important. Adequate control over arterial pressure and frequent monitoring of patients during the first days of antiangiogenic therapy is essential for early diagnosis of possible adverse events. .


CONTEXTO: Sunitinibe é uma droga antiangiogênica aprovada para tratamento de câncer renal metastático. Sua ação como inibidor de tirosina quinase de receptores de fatores de crescimento do endotélio vascular (VEGFR) e de outros receptores de angiogênese pode levar a eventos adversos como hipertensão e insuficiência cardíaca. No entanto, é escassa na literatura a associação da terapia com sunitinibe e dissecção aguda de aorta. RELATO DE CASO: Relatamos o caso de um paciente do sexo masculino de 68 anos com câncer renal metastático que desenvolveu dissecção aguda de aorta durante tratamento com sunitinibe. O paciente não tinha histórico prévio de hipertensão nem outro fator de risco para dissecção de aorta. Após diagnóstico da dissecção de aorta, a droga foi suspensa e o paciente foi submetido à colocação de endoprótese na aorta, evoluindo posteriormente com controle clínico da pressão arterial e nova terapia para câncer renal com tensirolimo, um inibidor da via proteína alvo da rapamicina em mamíferos (mTOR). CONCLUSÕES: A hipertensão é um evento comum com uso de drogas antiangiogênicas na oncologia. No entanto, é importante o conhecimento de outros eventos cardiovasculares graves, como dissecção aguda de aorta, que podem ocorrer nesses pacientes. Controle adequado da pressão arterial e monitorização frequente dos pacientes nos primeiros dias de terapia antiangiogênica são essenciais para diagnóstico precoce de possíveis eventos graves. .


Subject(s)
Aged , Humans , Male , Aneurysm, Dissecting/chemically induced , Angiogenesis Inhibitors/adverse effects , Aortic Aneurysm/chemically induced , Indoles/adverse effects , Pyrroles/adverse effects , Aneurysm, Dissecting , Aortic Aneurysm , Carcinoma, Renal Cell/drug therapy , Hypertension/chemically induced , Hypertension/complications , Kidney Neoplasms/drug therapy , Protein-Tyrosine Kinases/antagonists & inhibitors
6.
Article in English | WPRIM | ID: wpr-216626

ABSTRACT

BACKGROUND/AIMS: To investigate abnormalities in blood electrolyte levels during severe hypoglycemia in Korean patients with type 2 diabetes mellitus (T2DM) in a clinical setting. METHODS: Blood electrolyte levels in adult T2DM patients during severe hypoglycemia were collected from January 1, 2008 to December 31, 2012. Patients who maintained normal serum creatinine and blood urea nitrogen levels were utilized in the study. Severe hypoglycemia was defined as a condition requiring medical assistance, such as administering carbohydrates when serum glucose levels less than 70 mg/dL were observed, in conjunction with other symptoms of hypoglycemia. RESULTS: A total of 1,068 patients who visited the emergency room with severe hypoglycemia were screened, of which 219 patients were included in this study. The incidence of abnormal levels for any electrolyte was 47%. Hypokalemia ( 100 beats per minute) and severe hypertension (> or = 180/120 mmHg) were 30 mg/dL (range, 14 to 62) and 35 mg/dL (range, 10 to 69; p = 0.04), 18.8% and 7.2% (p = 0.02), and 20.8% and 10.2% (p = 0.05) in the hypokalemia and normokalemia groups, respectively. CONCLUSIONS: During severe hypoglycemia, hypokalemia occurred in 21.9% of T2DM patients and was associated with tachycardia and severe hypertension. Therefore, the results suggest that severe hypoglycemia may increase cardiovascular events in T2DM.


Subject(s)
Aged , Aged, 80 and over , Biomarkers/blood , Blood Glucose/drug effects , Diabetes Mellitus, Type 2/blood , Emergency Service, Hospital , Female , Humans , Hypertension/chemically induced , Hypoglycemia/blood , Hypoglycemic Agents/adverse effects , Hypokalemia/blood , Male , Middle Aged , Potassium/blood , Republic of Korea/epidemiology , Risk Factors , Severity of Illness Index , Tachycardia/chemically induced , Water-Electrolyte Balance/drug effects
7.
Article in English | WPRIM | ID: wpr-223783

ABSTRACT

Lead (Pb), mercury (Hg), and cadmium (Cd) are common heavy metal toxins and cause toxicological renal effects at high levels, but the relevance of low-level environmental exposures in the general population is controversial. A total of 1,797 adults who participated in the KNHANES (a cross-sectional nationally representative survey in Korea) were examined, and 128 of them (7.1%) had chronic kidney disease (CKD). Our study assessed the association between Pb, Hg, Cd exposure, and CKD. Blood Pb and Cd levels were correlated with CKD in univariate logistic regression model. However, these environmental heavy metals were not associated with CKD after adjustment for age, sex, BMI, smoking, hyperlipidemia, hypertension, diabetes, and these metals in multivariate logistic regression models. We stratified the analysis according to hypertension or diabetes. In the adults with hypertension or diabetes, CKD had a significant association with elevated blood Cd after adjustment, but no association was present with blood Pb and Hg. The corresponding odds ratio [OR] of Cd for CKD were 1.52 (95% confidence interval [CI], 1.05-2.19, P=0.026) in adults with hypertension and 1.92 (95% CI, 1.14-3.25, P=0.014) in adults with diabetes. Environmental low level of Pb, Hg, Cd exposure in the general population was not associated with CKD. However, Cd exposure was associated with CKD, especially in adults with hypertension or diabetes. This finding suggests that environmental low Cd exposure may be a contributor to the risk of CKD in adults with hypertension or diabetes.


Subject(s)
Adult , Cadmium/blood , Cross-Sectional Studies , Diabetes Mellitus/chemically induced , Environmental Exposure , Female , Humans , Hypertension/chemically induced , Kidney/drug effects , Lead/blood , Male , Mercury/blood , Metals, Heavy/poisoning , Middle Aged , Nutrition Surveys , Poisoning/epidemiology , Renal Insufficiency, Chronic/epidemiology , Republic of Korea , Surveys and Questionnaires , Young Adult
8.
Rev. AMRIGS ; 57(4): 273-277, out.-dez. 2013. tab, graf
Article in Portuguese | LILACS | ID: biblio-847109

ABSTRACT

Introdução: A hipertensão arterial sistêmica é um achado frequente entre mulheres que necessitem terapia hormonal (TH). Os objetivos deste estudo foram verificar as modificações do peso corporal, da pressão arterial sistêmica e dos lipídios em mulheres hipertensas usuárias de TH ao longo do tempo. Métodos: Estudo longitudinal prospectivo. Trinta e três mulheres hipertensas com sintomas vasomotores, que consultaram no Ambulatório de Ginecologia Endócrina e Menopausa do Hospital São Vicente de Paulo ­ Passo Fundo/ RS, a partir de janeiro de 1993, participaram do estudo. Receberam TH com estrogênio, ou estrogênio + progestogênio, via oral. Foram examinadas a cada seis meses e durante 10 anos. Verificaram-se a idade, peso corporal (kg), pressão arterial sistólica (PAS) e diastólica (PAD) (mmHg), classes de anti-hipertensivos utilizados, glicemia de jejum (mg/dL), colesterol total e frações (mg/ dL) e triglicerídeos (mg/dL). Compararam-se os valores basais, aos 5 e 10 anos de seguimento, através de testes pareados. Resultados: A idade média foi 48,4 ± 4,8 anos. Houve uma tendência de aumento da PAS aos 5 anos, p=0,054, seguida de uma diminuição aos 10 anos, p=0,003. A PAD diminuiu aos 10 anos, p=0.001. Houve um acréscimo de anti-hipertensivos aos 5 anos de seguimento (p<0,001). As variáveis peso corporal, lipídios e glicemia de jejum não se modificaram ao longo do tempo. Conclusões: O uso de TH oral em pacientes hipertensas requer controle e eventual ajuste anti-hipertensivo em 5 anos. Ao longo de 10 anos de uso, a pressão arterial e o peso corporal mantiveram-se estáveis (AU)


Introduction: High blood pressure is a common finding among women who require hormone replacement therapy (HRT). The aims of this study were to assess changes in body weight, blood pressure, and lipid profile over time in hypertensive women using HRT. Methods: Prospective longitudinal study. Thirty-three hypertensive women with vasomotor symptoms, consulting at the Clinic of Endocrine Gynecology and Menopause of Hospital São Vicente de Paulo in Passo Fundo-RS, as of January 1993 were enrolled. They received estrogen or estrogen + progestogen orally and were examined every six months for 10 years. Age, body weight (kg) , systolic (SBP) and diastolic (DBP ) blood pressure (mmHg), classes of antihypertensive drugs used, fasting plasma glucose (mg/dL), total cholesterol and fractions (mg/dL) and triglycerides (mg/dL) were recorded. We compared the baseline values with those at 5- and 10-year follow-up through paired tests. Results: Mean age was 48.4 ± 4.8 years. There was a trend of increase in SBP at 5 years, p = 0.054, followed by a decrease at 10 years, p = 0.003. DBP decreased at 10 years, p = 0.001. There was an increase of antihypertensive drugs at 5 years of follow-up (p < 0.001 ). Body weight, lipid profile and fasting glucose did not change over time. Conclusions: Over 10 years of use, blood pressure and body weight remained stable. The use of oral HRT in hypertensive patients requires control and possible antihypertensive adjustment at 5 years (AU)


Subject(s)
Humans , Female , Adult , Middle Aged , Arterial Pressure/drug effects , Body Weight Changes , Hormone Replacement Therapy/adverse effects , Hypertension/chemically induced , Longitudinal Studies , Postmenopause , Prospective Studies
9.
Arq. bras. cardiol ; 100(4): 339-346, abr. 2013. ilus, tab
Article in Portuguese | LILACS | ID: lil-674192

ABSTRACT

FUNDAMENTO: A hipertensão arterial é uma síndrome multifatorial, crônica, causada tanto por fatores congênitos ou adquiridos. OBJETIVO: Avaliar os efeitos do treinamento físico resistido (TR) sobre pressão arterial, reatividade e morfologia vascular de ratos hipertensos induzidos por L-NAME. MÉTODOS: Ratos Wistar machos (200-250 g) foram divididos em 3 grupos: normotenso sedentário (NS), hipertenso sedentário (HS) e hipertenso treinado (HT). A hipertensão foi induzida pela administração de L-NAME (40 mg/kg) na água de beber por 4 semanas. A pressão arterial foi avaliada antes e após o TR. O TR foi realizado utilizando 50% de 1RM, em 3 séries de 10 repetições, 3 vezes por semana, durante quatro semanas. A reatividade vascular foi mensurada em artéria mesentérica superior por curvas concentração resposta ao nitroprussiato de sódio (NPS) e fenilefrina (FEN). Além disso, foram realizadas análises histológicas e estereológicas. RESULTADOS: O TR inibiu o aumento das pressões arteriais média e diastólica. Foi observada uma redução significativa na resposta máxima e na potência da FEN entre os grupos HS e HT. A análise histológica evidenciou aspecto normal para as túnicas íntima, média e adventícia em todos os grupos. Não houve diferença significativa nas áreas do lúmen, da túnica média e total das artérias dos grupos HS e HT em relação ao NS. A razão parede/lúmen arterial do grupo HS apresentou diferença significativa em relação ao NS (p < 0,05), mas esta não foi diferente do HT. CONCLUSÕES: O TR foi capaz de prevenir a elevação da pressão arterial sob as condições deste estudo. Este controle parece envolver a regulação de mecanismo vasoconstritor e a manutenção do diâmetro luminal de ratos hipertensos induzidos por L-NAME.


BACKGROUND: Arterial hypertension is a multifactorial chronic condition caused by either congenital or acquired factors. OBJECTIVE: To evaluate the effects of Resistance Training (RT) on arterial pressure, and on vascular reactivity and morphology, of L-NAME-treated hypertensive rats. METHODS: Male Wistar rats (200 - 250 g) were allocated into Sedentary Normotensive (SN), Sedentary Hypertensive (SH) and Trained Hypertensive (TH) groups. Hypertension was induced by adding L-NAME (40 mg/Kg) to the drinking water for four weeks. Arterial pressure was evaluated before and after RT. RT was performed using 50% of 1RM, 3 sets of 10 repetitions, 3 times per week for four weeks. Vascular reactivity was measured in rat mesenteric artery rings by concentration-response curves to sodium nitroprusside (SNP); phenylephrine (PHE) was also used for histological and stereological analysis. RESULTS: Resistance training inhibited the increase in mean and diastolic arterial pressures. Significant reduction was observed in Rmax (maximal response) and pD2 (potency) of PHE between SH and TH groups. Arteries demonstrated normal intima, media and adventitia layers in all groups. Stereological analysis demonstrated no significant difference in luminal, tunica media, and total areas of arteries in the SH and TH groups when compared to the SN group. Wall-to-lumen ratio of SH arteries was significantly different compared to SN arteries (p<0.05) but there was no difference when compared to TH arteries. CONCLUSIONS: RT was able to prevent an increase in blood pressure under the conditions in this study. This appears to involve a vasoconstrictor regulation mechanism and maintenance of luminal diameter in L-NAME induced hypertensive rats.


Subject(s)
Animals , Male , Rats , Blood Pressure/physiology , Hypertension/metabolism , Physical Conditioning, Animal/methods , Resistance Training , Vasoconstriction/physiology , Analysis of Variance , Blood Pressure/drug effects , Disease Models, Animal , Hypertension/chemically induced , Hypertension/pathology , Mesenteric Artery, Superior/physiology , NG-Nitroarginine Methyl Ester , Nitroprusside/pharmacology , Phenylephrine/pharmacology , Random Allocation , Rats, Wistar , Vasoconstrictor Agents/pharmacology , Vasodilator Agents/pharmacology
10.
Pakistan Journal of Pharmaceutical Sciences. 2013; 26 (5): 1013-1022
in English | IMEMR | ID: emr-138424

ABSTRACT

The purpose of the study is evaluation and assessment of parameters of cardiac toxicity in patients subjected to 5-FU based chemotherapy. Cardiac morbidity is a reported outcome in different 5FU/LV regimens; however none of them are definite or proximate. The bimonthly regimen of high dose leucovorin is reported to be less toxic and more effective as compared to the monthly regimen of low dose leucovorin. We report the detailed assessment of few cardiac parameter of toxicity in patients of advanced colorectal carcinoma subjected to two Schedules of high and low dose Folinic Acid, 5-Fluorouracil, bolus and continuous infusion. The correlation of elevated cardiac biomarkers, angina and hypertension is comparatively assessed in patients with normal general status, hyperglycemia and known cardiac disorders subjected to two different 5FU based chemotherapeutic regimen


Subject(s)
Humans , Female , Male , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Carcinoma/drug therapy , Hypertension/chemically induced , Leucovorin/adverse effects , Heart Diseases/chemically induced , Fluorouracil/adverse effects , Biomarkers/blood , Blood Pressure/drug effects , Prospective Studies , Risk Factors , Time Factors , Treatment Outcome
11.
Arq. bras. cardiol ; 99(6): 1082-1091, dez. 2012. ilus, graf, tab
Article in Portuguese | LILACS | ID: lil-662371

ABSTRACT

FUNDAMENTO: O Imatinib é um inibidor do receptor tirosina-quinase que foi confirmada como exercendo um efeito inibidor sobre a atividade do receptor do PDGF, fator de crescimento plaquetário (PDGFRα e PDGFRβ). OBJETIVO: Investigar o efeito protetor do Imatinib na fibrose miocárdica em acetato de deoxicorticosterona (DOCA)/ratos com hipertensão induzida por sal. MÉTODOS: Sessenta ratos Sprague-Dawley machos, uninefrectomizados foram distribuídos em três grupos: ratos controles (grupo CON): grupo deoxicorticosterona (grupo DOCA); grupo deoxicorticosterona e Imatinib (grupo DOCA IMA). A Pressão Arterial Sistólica (PAS) foi medida quinzenalmente. Foi estudada a porção apical do ventrículo esquerdo. Foram empregados: coloração vermelho sirius, coloração de hematoxilina-eosina, imuno-histoquímica e ensaio de western blot. RESULTADOS: A PAS nos grupos DOCA e IMA+DOCA foi maior que no grupo CON nos dias 14 e 28. Os animais do grupo DOCA apresentaram fibrose intersticial e perivascular grave no dia 28, e as expressões de PI, PIII, tenascina-C e fibronectina foram significativamente maiores que nos grupos DOCA+IMA e CON. Quando comparados com o grupo CON, os grupos DOCA e DOCA+IMA apresentaram resposta inflamatória de tecido miocárdico e infiltração de monócitos/macrófagos de diferentes graus. As expressões proteicas do PDGF-A, PDGF-C e PDGFRα foram significativamente maiores nos grupos DOCA e DOCA+IMA que no grupo CON, mas a expressão proteica do p-PDGFRα no grupo DOCA+IMA foi menor que no DOCA. CONCLUSÃO: O Imatinib pode exercer efeitos inibitórios sobre a fibrose miocárdica em ratos com hipertensão induzida por DOCA/sal, os quais podem ser atribuídos à inibição da atividade do PDGFR-α.


BACKGROUND: Imatinib is a tyrosine kinase receptor inhibitor that has been confirmed to exert inhibitory effect on the platelet derived growth factor PDGF receptor (PDGFRα and PDGFRβ) activity. OBJECTIVE: To investigate the protective effect of imatinib on the myocardial fibrosis in deoxycorticosterone-acetate (DOCA)/salt induced hypertensive rats. METHODS: Sixty male uninephrectomized Sprague-Dawley rats were assigned to three groups: control rats (CON group); deoxycorticosterone group (DOCA group); deoxycorticosterone and imatinib group (DOCA+IMA group). Systolic blood pressure (SBP) was measured biweekly. The apical portion of the left ventricle was studied. Sirius-Red staining, Hematoxylin-Eosin staining, immunohistochemistry and Western blot assay were employed. RESULTS: SBP in the DOCA group and DOCA+IMA group was higher than that in the CON group on day 14 and 28. Animals in the DOCA group showed severe interstitial and perivascular fibrosis on day 28, and the expressions of PI, PIII, tenascin-C and fibronectin were significantly higher than those in the DOCA+IMA group and CON group. When compared with the CON group, myocardial tissue inflammatory response and monocyte/macrophage infiltration of different degrees were observed in the DOCA group and DOCA+IMA group. Protein expressions of PDGF-A, PDGF-C and PDGFRα were signiflcantly higher in the DOCA and DOCA+IMA groups than those in the CON group, but the p-PDGFRα protein expression in the DOCA+IMA group was lower than that in the DOCA group. CONCLUSION: Imatinib can exert inhibitory effects on myocardial fibrosis in DOCA/salt induced hypertensive rats, which may be attributed to the inhibition of PDGFR-α activity.


Subject(s)
Animals , Male , Rats , Benzamides/pharmacology , Endomyocardial Fibrosis/drug therapy , Piperazines/pharmacology , Protein Kinase Inhibitors/pharmacology , Pyrimidines/pharmacology , Receptor, Platelet-Derived Growth Factor alpha/antagonists & inhibitors , Blotting, Western , Benzamides/therapeutic use , Blood Pressure/drug effects , Desoxycorticosterone , Disease Models, Animal , Endomyocardial Fibrosis/pathology , Fibronectins/analysis , Fibronectins/metabolism , Fibrosis/drug therapy , Fibrosis/pathology , Hypertension/chemically induced , Hypertension/physiopathology , Nephrectomy/methods , Piperazines/therapeutic use , Protein Kinase Inhibitors/therapeutic use , Pyrimidines/therapeutic use , Rats, Sprague-Dawley , Receptor, Platelet-Derived Growth Factor alpha/metabolism , Receptor, Platelet-Derived Growth Factor beta/antagonists & inhibitors , Receptor, Platelet-Derived Growth Factor beta/metabolism , Treatment Outcome , Tenascin/analysis , Tenascin/metabolism
12.
Arch. cardiol. Méx ; 82(4): 312-319, oct.-dic. 2012. ilus, tab
Article in Spanish | LILACS | ID: lil-695068

ABSTRACT

La hipertensión arterial sistémica es un problema de salud pública. Esta entidad afecta al 43% de la población mexicana y es considerada una de los principales factores de riesgo para el desarrollo de eventos vasculares cerebrales, insuficiencia cardiaca e insuficiencia renal. La prevalencia de hipertensión arterial sistémica se ha incrementado durante las últimas décadas debido a la adopción de una dieta alta en sal. Existe evidencia de que la hipertensión sensible a sal se acompaña de alteraciones estructurales renales como dilatación tubular, fibrosis intersticial en parches, expresión de osteopontina e infiltrado túbulo intersticial de linfocitos y macrófagos, que impiden una excreción urinaria de sodio adecuada y en consecuencia, favorecen el desarrollo de HAS. De forma experimental se ha demostrado que estas alteraciones estructurales tienen una naturaleza inflamatoria y que la administración de medicamentos inmunosupresores disminuye la lesión tisular y mejoran el control de la presión arterial. En conjunto, los conocimientos derivados de los estudios de hipertensión sensible a sal pueden derivar en el desarrollo de nuevos fármacos destinados a mejorar el pronóstico asociado a la hipertensión arterial sistémica.


High blood pressure is a public health problem. This entity affects 43% of the mexican population and is considered a major risk factor for development of stroke, cardiac failure and chronic kidney disease. Hypertension prevalence has increased over the last decades, mainly because of high salt diet. There is evidence showing that salt-sensitive hypertension develops structural changes as tubular dilation, patchy interstitial fibrosis, osteopontin expression and lymphocytic/macrophage tubulointerstitial infiltrate that blunts urinary sodium excretion and therefore promotes HBP. It has been shown that this structural damage has an inflammatory origin and that immunosuppresant drugs down-regulates tissular injury and improves blood pressure control. In summary, this salt-sentitive hypertension data can be used in development of new and potent blood pressure drugs.


Subject(s)
Humans , Hypertension/chemically induced , Hypertension/immunology , Inflammation/complications , Lymphocytes/physiology , Macrophages/physiology , Sodium Chloride, Dietary/adverse effects
13.
Arq. bras. cardiol ; 99(2): 724-731, ago. 2012. ilus, tab
Article in Portuguese | LILACS | ID: lil-647713

ABSTRACT

FUNDAMENTO: A felipressina foi adicionada ao anestésico local para aumentar a duração do efeito anestésico e reduzir a toxicidade nos procedimentos dentários. No entanto, o efeito sobre a pressão arterial é incerta, e isso pode ser altamente relevante no tratamento dentário de pacientes hipertensos. OBJETIVO: Investigar o efeito da felipressina sobre a pressão arterial em pacientes hipertensos com pressão arterial controlada. MÉTODOS: Foram estudados 71 indivíduos com essas características e com necessidade de tratamento periodontal. Após 10 minutos de repouso, a anestesia local (prilocaína) foi infiltrada com e sem adição de felipressina. Em seguida, uma raspagem subgengival profunda foi realizada. A pressão arterial foi medida por um equipamento oscilométrico automático (DIXTAL DX2010). Dez minutos após a administração do anestésico, o pico de ação anestésica foi gravado. O Inventário de Ansiedade Traço-Estado (IDATE) foi utilizado para avaliar o traço de ansiedade nos pacientes. RESULTADOS: A pressão arterial sistólica aumentou após a anestesia, independentemente da associação com felipressina, durante todo o procedimento dentário (p < 0,05), e essa resposta pode ser explicada, pelo menos em parte, pelos níveis de traço de ansiedade dos indivíduos. No entanto, um aumento adicional na pressão arterial diastólica foi observado quando a prilocaína foi associada a felipressina (p < 0,05), mas essa resposta não se alterou com os níveis de traço de ansiedade. CONCLUSÃO: A felipressina aumentou a pressão arterial diastólica de pacientes hipertensos com pressão arterial controlada. Pacientes com traço de ansiedade elevado apresentaram aumento na pressão arterial sistólica em alguns procedimentos, sugerindo que um aumento da pressão arterial também pode estar relacionado ao medo ou à ansiedade.


BACKGROUND: Felypressin has been added to local anesthetic to increase the length of the anesthetic effect and reduce toxicity during dental procedures. However, the effect on blood pressure remains uncertain, and this may be highly relevant in the dental treatment of hypertensive patients. OBJECTIVE: To investigate the effect of felypressin on blood pressure in hypertensive patients with controlled BP. METHODS: 71 subjects with these characteristics and in need of periodontal treatment were studied. After 10 minutes of rest, local anesthesia (prilocaine) was infiltrated with and without addition of felypressin. Then, a deep subgingival scaling was performed. Blood pressure was measured by an automated oscillometric device (DIXTAL DX2010). Ten minutes after the administration of the anesthetic, peak anesthetic action was recorded. The State-Trait Anxiety Inventory (STAI) was used to assess the patients' trait anxiety. RESULTS: Systolic blood pressure increased after anesthesia, regardless of association with felypressin, throughout the dental procedure (p<0.05) and this response can be explained, at least in part, by the trait anxiety levels of the subjects. However, a further increase in diastolic blood pressure was observed when prilocaine was associated with felypressin (p<0.05), but this response did not change with trait anxiety levels. CONCLUSION: Felypressin increased the diastolic blood pressure of hypertensive patients with controlled blood pressure. Patients with high trait anxiety presented increases in systolic blood pressure upon some procedures, suggesting that an increase in blood pressure might also be related to fear or anxiety.


Subject(s)
Adult , Female , Humans , Male , Middle Aged , Anesthesia, Dental/adverse effects , Blood Pressure/drug effects , Felypressin/adverse effects , Hypertension/chemically induced , Vasoconstrictor Agents/adverse effects , Analysis of Variance , Anxiety/psychology , Hypertension/psychology , Periodontal Diseases/therapy , Statistics, Nonparametric , Time Factors
14.
Rev. chil. cardiol ; 31(3): 202-214, 2012. ilus, tab
Article in Spanish | LILACS | ID: lil-670191

ABSTRACT

Resumen: La enzima convertidora de angiotensina I (ECA2) a través de Angiotensina (Ang)-(1-9) más que Ang-(1-7) contrarresta los efectos deletéreos de ECA y Ang II. Se desconoce si Ang-(1-9) es efectiva en el tratamiento del remodelamiento cardiovascular (RMCV) hipertensivo, en ratas con polimorfismo del gen de la ECA. Objetivo: Determinar el efecto de Ang-(1-9) en el tratamiento del RMCV hipertensivo en ratas con niveles genéticamente determinados de ECA y Ang II. Métodos: Ratas normotensas homocigotas, Lewis (LL) y Brown Norway (BN), se les indujo HTA a través del modelo Goldblatt (GB, 2 riñones-1 pinzado). Después de 4 semanas, las ratas hipertensas se rando-mizaron para recibir Ang-(1-9) (602 ng/Kg min) o una coadministración de Ang-(1-9)+A779 (100 ng/Kg min, antagonista del receptor MAS de Ang-(1-7)) durante 14 días mediante una minibomba. Como controles se usaron ratas sometidas a operación ficticia (Sham). Se determinó masa corporal (MC), presión arterial sistólica (PAS), masa ventricular (MV), área de cardiomiocitos (AC), área y grosor de la túnica media (ATM, GTM), fracción volumétrica de colágeno total (FVCT) en el ventrículo izquierdo (VI), niveles proteicos de colágeno tipo I (Col I) en la aorta (Ao) y la infiltración de macrófagos en Ao y VI, por medio de su molécula especifica ED1 (ED1-Ao, ED1-VI). Resultados: La administración de Ang-(1-9) disminuyó significativamente PAS, MV, AC, FVCT, Col I, ATM, GTM, ED1-Ao (-) y ED1-VI, en las ratas hipertensas LL y BN respecto a las ratas GB sin tratamiento, respectivamente. Este efecto no fue inhibido por el antagonista A779. El polimorfismo de la ECA no modificó la respuesta al tratamiento. Conclusión: Ang-(1-9) redujo eficazmente la HTA y el RMCV secundario, independiente al polimorfismo en el gen de la ECA. Este efecto posiblemente es directo ya que no fue mediado por Ang-(1-7). Fondecyt 1100874.


Background: The angiotensin I converting enzyme 2 (ACE2) counteracts the deleterious effects of ACE and Ang II through angiotensin (Ang) -(1-9) rather than Ang-(1-7). In addition, it is not clear whether Ang-(1-9) is effective in the reversal of hypertensive cardiovascular remodeling (CVRM) in rats with ACE gene polymorphism. Objective: To determine the effect of Ang-(1-9) in the prevention of hypertensive CVRM in rats with genetically determined levels of ACE and Ang II. Methods: In normotensive homozygous Lewis (LL) and Brown Norway (BN) rats hypertension was induced by the Goldblatt 2 kidney-1 pinch model. After 4 weeks, rats were randomized to receive Ang- (1-9) (602 ng / Kg min) or the co administration of Ang- (19) + A779 (100 ng / kg min, a MAS receptor antagonist of Ang- (1-7)) for 14 days. Sham operated rats were used as controls. We determined body mass (BM), systolic blood pressure (SBP), ventricular mass (VM), cardiomyocyte area (CA), area and thickness of the aortic media (ATM, TTM), LV total collagen volume fraction (FVCT), type I collagen protein levels (Col I) in the aorta (Ao) and macrophage infiltration in LV and Ao, through its specific molecule ED1 (ED1-Ao, ED1-VI). Results: Continuous administration of Ang- (1-9) significantly decreased SBP, VM, CA, TCVF, Col I, TTM, and ED1 in the aorta and left ventricle of hypertensive rats. This effect was not inhibited by the antagonist A779. ACE polymorphism did not modify the response to treatment. Conclusion: Ang- (1-9) effectively reduced hypertension induced CVRM independent of ACE gene polymorphism. This effect was not mediated by Ang- (1-7).


Subject(s)
Animals , Rats , Hypertension/chemically induced , Peptidyl-Dipeptidase A/administration & dosage , Peptidyl-Dipeptidase A/genetics , Cardiovascular System/pathology , Polymorphism, Genetic , Cardiovascular System/enzymology
15.
Clinics ; 67(5): 489-496, 2012. graf, tab
Article in English | LILACS | ID: lil-626346

ABSTRACT

OBJECTIVES: Tension cost, the ratio of myosin ATPase activity to tension, reflects the economy of tension development in the myocardium. To evaluate the mechanical advantage represented by the tension cost, we studied papillary muscle contractility and the activity of myosin ATPase in the left ventricles in normal and pathophysiological conditions. METHODS: Experimental protocols were performed using rat left ventricles from: (1) streptozotocin-induced diabetic and control Wistar rats; (2) N-nitro-L-arginine methyl ester (L-NAME) hypertensive and untreated Wistar rats; (3) deoxycorticosterone acetate (DOCA) salt-treated, nephrectomized and salt- and DOCA-treated rats; (4) spontaneous hypertensive rats (SHR) and Wistar Kyoto (WKY) rats; (5) rats with myocardial infarction and shamoperated rats. The isometric force, tetanic tension, and the activity of myosin ATPase were measured. RESULTS: The results obtained from infarcted, diabetic, and deoxycorticosterone acetate-salt-treated rats showed reductions in twitch and tetanic tension compared to the control and sham-operated groups. Twitch and tetanic tension increased in the N-nitro-L-arginine methyl ester-treated rats compared with the Wistar rats. Myosin ATPase activity was depressed in the infarcted, diabetic, and deoxycorticosterone acetate salt-treated rats compared with control and sham-operated rats and was increased in N-nitro-L-arginine methyl ester-treated rats. These parameters did not differ between SHR and WKY rats. In the studied conditions (e.g., post-myocardial infarction, deoxycorticosterone acetate salt-induced hypertension, chronic N-nitro-L-arginine methyl ester treatment, and streptozotocin-induced diabetes), a positive correlation between force or plateau tetanic tension and myosin ATPase activity was observed. CONCLUSION: Our results suggest that the myocardium adapts to force generation by increasing or reducing the tension cost to maintain myocardial contractility with a better mechanical advantage.


Subject(s)
Animals , Male , Rats , Diabetes Mellitus, Experimental/physiopathology , Hypertension/physiopathology , Myocardial Contraction/physiology , Myocardial Infarction/physiopathology , Papillary Muscles/physiopathology , Ventricular Function, Left , Ventricular Myosins/metabolism , Desoxycorticosterone/analogs & derivatives , Diabetes Mellitus, Experimental/chemically induced , Enzyme Inhibitors , Hypertension/chemically induced , Myocardial Contraction/drug effects , Nephrectomy , NG-Nitroarginine Methyl Ester , Rats, Inbred SHR , Rats, Inbred WKY
16.
Braz. j. med. biol. res ; 44(9): 933-938, Sept. 2011. ilus
Article in English | LILACS | ID: lil-599668

ABSTRACT

Ouabain, an endogenous digitalis compound, has been detected in nanomolar concentrations in the plasma of several mammals and is associated with the development of hypertension. In addition, plasma ouabain is increased in several hypertension models, and the acute or chronic administration of ouabain increases blood pressure in rodents. These results suggest a possible association between ouabain and the genesis or development and maintenance of arterial hypertension. One explanation for this association is that ouabain binds to the α-subunit of the Na+ pump, inhibiting its activity. Inhibition of this pump increases intracellular Na+, which reduces the activity of the sarcolemmal Na+/Ca2+ exchanger and thereby reduces Ca2+ extrusion. Consequently, intracellular Ca2+ increases and is taken up by the sarcoplasmic reticulum, which, upon activation, releases more calcium and increases the vascular smooth muscle tone. In fact, acute treatment with ouabain enhances the vascular reactivity to vasopressor agents, increases the release of norepinephrine from the perivascular adrenergic nerve endings and promotes increases in the activity of endothelial angiotensin-converting enzyme and the local synthesis of angiotensin II in the tail vascular bed. Additionally, the hypertension induced by ouabain has been associated with central mechanisms that increase sympathetic tone, subsequent to the activation of the cerebral renin-angiotensin system. Thus, the association with peripheral mechanisms and central mechanisms, mainly involving the renin-angiotensin system, may contribute to the acute effects of ouabain-induced elevation of arterial blood pressure.


Subject(s)
Animals , Humans , Rats , Blood Pressure/drug effects , Cardiotonic Agents/pharmacology , Hypertension/chemically induced , Ouabain/pharmacology , Angiotensin II/biosynthesis , Calcium/metabolism , Cardiotonic Agents/administration & dosage , Cardiotonic Agents/metabolism , Central Nervous System/drug effects , Hypertension/metabolism , Injections, Intravenous , Norepinephrine , Ouabain/administration & dosage , Ouabain/metabolism , Peptidyl-Dipeptidase A/metabolism , Renin-Angiotensin System/drug effects , Sodium-Potassium-Exchanging ATPase/drug effects , Sodium-Potassium-Exchanging ATPase/physiology
17.
Medicina (B.Aires) ; 71(3): 207-210, jun. 2011. graf
Article in Spanish | LILACS | ID: lil-633848

ABSTRACT

El conocimiento de las diversas vías de oncogénesis ha llevado al desarrollo en los últimos cinco años de nuevas terapias para el tratamiento del cáncer renal avanzado, las que poseen como blanco al factor derivado del endotelio vascular (VEGF) y sus receptores (antiangiogénicos) y al blanco mamífero de la rapamicina (mTOR). Los antiangiogénicos constituyen un grupo de moléculas activas con un espectro de toxicidad peculiar que comprende el desarrollo de hipertensión arterial, disfunción tiroidea y síndrome de mano-pie. La identificación de factores predictivos clínicos y moleculares lograría identificar aquellos pacientes que se beneficiarían con dicho tratamiento, evitando exposición y toxicidad innecesaria al resto. La aparición de hipertensión arterial se ha correlacionado con respuesta al tratamiento y eficacia clínica. En nuestra serie retrospectiva, los pacientes tratados con antiangiogénicos que desarrollaron hipertensión arterial tuvieron aumento de la tasa de respuestas e intervalo libre de enfermedad en comparación con aquellos que, tratados de la misma manera, no manifestaron hipertensión. La hipertensión arterial debería considerarse como un factor predictor clínico en su tratamiento. Dichos hallazgos deberían ser corroborados en forma prospectiva y con un mayor número de pacientes.


Knowledge of several pathways of oncogenesis has led to the development of novel therapies in the treatment of advanced kidney cancer in the last five years. These have targeted the vascular endothelium-derived factor (VEGF) (angiogenesis) and mammalian target of rapamycin (mTOR). Antiangiogenics are a group of active molecules with a peculiar spectrum of toxicity including the development of hypertension, thyroid dysfunction and hand-foot syndrome. The identification of molecular and clinical predictors would allow to identify those patients who would benefit from such treatment and saveguarding the rest from toxic exposure. The occurrence of hypertension has been correlated with treatment response and clinical efficacy. In our retrospective series, patients treated with antiangiogenic agents who developed high blood pressure showed a higher response rate and disease-free interval compared to those without increased blood pressure. Hypertension should be considered a clinical predictor in the treatment of these patients. These findings should be confirmed in a larger study population.


Subject(s)
Adult , Aged , Female , Humans , Male , Middle Aged , Angiogenesis Inhibitors/adverse effects , Carcinoma, Renal Cell/drug therapy , Hypertension/chemically induced , Kidney Neoplasms/drug therapy , Angiogenesis Inhibitors/therapeutic use , Predictive Value of Tests , Retrospective Studies , Treatment Outcome
18.
Arq. bras. cardiol ; 96(4): e81-e89, abr. 2011. tab
Article in Portuguese | LILACS | ID: lil-585904

ABSTRACT

A contracepção hormonal é o método mais utilizado para prevenção de gestações não planejadas. A literatura tem demonstrado associação entre risco cardiovascular e uso de hormonioterapia. A fim de melhorar a orientação contraceptiva para mulheres com fatores de risco para doença cardiovascular, realizamos uma revisão da literatura em relação ao assunto. Esta revisão descreve os dados mais recentes da literatura científica acerca da influência dos contraceptivos hormonais em relação a trombose venosa, arterial e hipertensão arterial sistêmica, doenças cada dia mais prevalentes na população feminina jovem.


Hormonal contraception is the most widely used method to prevent unplanned pregnancies. The literature has shown an association between cardiovascular risk and use of hormone therapy. With the purpose of providing better guidelines on contraception methods for women with risk factors for cardiovascular disease, we have reviewed the literature on the subject. This review describes the latest data from the scientific literature concerning the influence of hormonal contraceptives on arterial thrombosis, venous thrombosis and systemic high blood pressure, which are diseases that have become increasingly prevalent among young females.


La contracepción hormonal es el método más utilizado para la prevención de los embarazos no planificados. La literatura ha venido demostrando la asociación que existe entre el riesgo cardiovascular y el uso de la hormonoterapia. Con el objetivo de mejorar la orientación en la contracepción en mujeres con factores de riesgo para el desarrollo de enfermedad cardiovascular, realizamos una revisión de la literatura con relación a ese asunto. Esa revisión describe los datos más recientes de la literatura científica acerca de la influencia de los anticonceptivos hormonales con relación a la trombosis venosa, arterial e hipertensión arterial sistémica, enfermedades cada día más prevalentes en la población femenina joven.


Subject(s)
Female , Humans , Cardiovascular System/drug effects , Contraceptives, Oral, Hormonal/adverse effects , Hypertension/chemically induced , Thrombosis/chemically induced , Cardiovascular Diseases/chemically induced , Contraceptives, Oral, Hormonal , Risk Factors
19.
Rio de Janeiro; s.n; 2011. 84 p. ilus, tab.
Thesis in Portuguese | LILACS | ID: lil-681500

ABSTRACT

Este trabalho teve como objetivo investigar os efeitos da telmisartana (agonista PPAR-gama parcial), losartana (puro bloqueador do receptor AT1 da angiotensina II) e rosiglitazona (agonista PPAR-gama) em modelo experimental de síndrome metabólica. Os alvos do estudo foram a pressão arterial, metabolismo de carboidratos, resistência insulínica, inflamação, tecido adiposo e fígado. Camundongos C57BL/6 (a partir de 3 meses de idade) foram alimentados com dieta padrão (SC, n = 10) ou dieta hiperlipídica rica em sal (HFHS, n = 40) por 12 semanas. Após esse tempo, os animais do grupo HFHS foram subdivididos em 4 grupos (n = 10): HFHS (sem tratamento), ROSI (HFHS tratado com rosiglitazona), TELM (HFHS tratado com telmisartana) e LOS (HFHS tratado com losartana) por 5 semanas. O grupo HFHS apresentou um significante ganho de peso e aumento da pressão arterial sistólica, hiperinsulinemia com resistência insulínica, hiperleptinemia, hipertrofia de adipócitos bem como um quadro de esteatose hepática e níveis aumentados da citocina inflamatória interleucina-6 (IL-6). Os animais tratados com telmisartana chegou ao final do experimento com massa corporal similar ao grupo SC, com reversão do quadro de resistência insulínica, com pressão arterial normal, adipócitos de tamanho normal e sem apresentar esteatose hepática. Além disso, o tratamento com telmisartana aumentou a expressão de PPARγ e adiponectina no tecido adiposo epididimal. A expressão da proteína desacopladora-1 (UCP-1) no tecido adiposo branco (TAB) também foi aumentada. O tratamento com losartana diminuiu a pressão arterial para valores normais, porém com menores efeitos nos parâmetros metabólicos dos animais. O presente modelo experimental de ganho de peso e hipertensão induzidos por dieta mimetiza a síndrome metabólica humana. Neste modelo, a telmisartana aumentou a expressão de UCP-1 no TAB, preveniu o ganho de peso e melhorou a sensibilidade à insulina e a esteatose hepática dos camundongos C57BL/6...


The study aimed to investigate the effects of telmisartan (a partial PPAR gamma agonist), losartan (a pure angiotensin II receptor blocker) and rosiglitazone (PPAR gamma agonist) in a mice model of metabolic syndrome (MetS). The targets of this study were blood pressure (BP), carbohydrate metabolism, insulin resistance, inflammation, white adipose tissue (WAT) and liver. Male C57BL/6 mice were studied over 17 weeks after being separated into two major groups according to diet: standard chow (SC, 10% fat, n = 10) or high-fat high-salt chow (HFHS, 60% fat, 7% salt, n = 40). In the last 5 weeks of the experiment, the HFHS group was divided into four groups (n = 10): untreated HFHS, ROSI (HFHS plus rosiglitazone), TELM (HFHS plus telmisartan), and LOS (HFHS plus losartan). The HFHS group had significantly greater body mass and BP, in addition to hyperinsulinemia with insulin resistance, hyperleptinemia, adipocyte hypertrophy and hepatic steatosis as well as increased inflammatory cytokine levels. Animals treated with telmisartan had body weights similar to the SC group, in addition to reversed insulin resistance, reduced hypertension, reduced adipocyte hypertrophy, ameliorates hepatic steatosis and decreased IL-6. Telmisartan increased PPARγ and adiponectin expression in white adipose tissue. Interestingly, the expression of UCP-1 in white adipose tissue was also increased by treatment with telmisartan. Losartan decreased BP but had smaller effects on metabolic parameters. The present model of diet-induced weight gain and hypertension in mice mimics human features of MetS. In this model, telmisartan enhances UCP-1 expression in WAT, prevented weight gain and ameliorates insulin sensitivity and hepatic steatosis in C57Bl/6 mice, probably due to PPAR gamma activation.


Subject(s)
Animals , Rats , Angiotensin II Type 1 Receptor Blockers , PPAR gamma/agonists , Metabolic Syndrome/drug therapy , Liver/physiopathology , Hypertension/chemically induced , Insulin Resistance , Sodium, Dietary/administration & dosage , Adipose Tissue/physiopathology , Weight Gain
20.
Acta cir. bras ; 26(supl.1): 57-59, 2011. graf
Article in English | LILACS | ID: lil-600659

ABSTRACT

PURPOSE: To evaluate the effect of Rut-bpy (Cis-[Ru(bpy)2(SO3)(NO)]PF 6), a novel nitric oxide donor in Nω-nitro-L-arginine methyl ester (L-NAME)-induced hypertensive rats. METHODS: Twenty-four male Wistar rats were randomly assigned to four groups (n=6), named according to the treatment applied (G1-Saline, G2-Rut-bpy, G3-L-NAME and G4-L-NAME+Rut-bpy). L-NAME (30 mg/Kg) was injected intraperitoneally 30 minutes before the administration of Rut-bpy (100 mg/Kg). Mean abdominal aorta arterial blood pressure (MAP) was continuously monitored. RESULTS: Mean arterial blood pressure (MAP) in G3 rats rose progressively, reaching 147±16 mmHg compared with 100±19 mm Hg in G1 rats (p<0.05). In G4 rats, treated with L-NAME+Rut-bpy, MAP reached 149+11 mm Hg while in G2 rats, treated with Rut-bpy, MAP values were 106±11 mm Hg. In G1 rats these values decreased progressively reaching 87+14 mm Hg after 30 minutes. An important finding was the maintenance of the MAP throughout the experiment in G2 rats. CONCLUSION: Rut-bpy does not decrease the MAP in L-Name induced hypertensive rats. However, when it is used in anesthetized hypotensive rats a stable blood pressure is obtained.


OBJETIVO: Avaliar o efeitos do Rut-bpy (Cis-[Ru (bpy)2(SO3)(NO)] PF6), um novo doador de óxido nítrico, em ratos hipertensos induzidos pelo éster metílico de N-nitro-L-arginina (L-NAME). MÉTODOS: Vinte e quatro ratos Wistar machos foram distribuídos aleatoriamente em quatro grupos (n = 6), nomeados de acordo com o tratamento aplicado (G1-Salina, G2-Rut-bpy, G3-L-NAME e G4-L-NAME+Rut -bpy). L-NAME (30 mg / Kg) foi injetado por via intraperitoneal 30 minutos antes da administração de Rut-bpy (100 mg / kg). A pressão arterial média (PAM) da aorta abdominal foi monitorada continuamente. RESULTADOS: A pressão arterial média (PAM) em ratos do grupo G3 subiu progressivamente, chegando a 147 ±16 mm Hg, em comparação com 100 ±19 mm Hg em ratos do G1 (p <0,05). Em ratos G4, tratados com L-NAME + Rut-bpy, a PAM atingiu 149±11 milímetros de Hg, enquanto no G2 (ratos tratados com Rut bpy) os valores da PAM foram 106 ±11 mm Hg. No G1 esses valores decresceram progressivamente, atingindo 87±14 mm Hg após 30 minutos. Um achado importante foi a manutenção da PAM durante todo o experimento em ratos do grupo G2. CONCLUSÃO: O uso de Rut bpy não diminui a PAM em ratos hipertensos por L-NAME. No entanto, quando ele é usado em ratos anestesiados, hipotensos, uma pressão arterial estável é obtida.


Subject(s)
Animals , Male , Rats , Blood Pressure/drug effects , Coordination Complexes/pharmacology , Hypertension/drug therapy , Nitric Oxide Donors/pharmacology , Organometallic Compounds/pharmacology , Ruthenium/pharmacology , Vasodilator Agents/pharmacology , Anesthesia , Blood Pressure/physiology , Disease Models, Animal , Hypertension/chemically induced , Hypertension/metabolism , NG-Nitroarginine Methyl Ester , Nitric Oxide/biosynthesis , Organometallic Compounds/metabolism , Random Allocation , Rats, Wistar , Ruthenium/metabolism , Treatment Outcome , Vasodilator Agents/metabolism
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