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1.
Int J Sports Med ; 2024 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-38986487

RESUMO

It is well known that cardiometabolic dysfunction gradually increases after menopause and the sedentary lifestyle can aggravated this condition. Therefore, we compared the effects of prior aerobic exercise training in premenopausal period and after ovariectomy (OVX) on metabolic, hemodynamic and autonomic parameters in experimental model of menopause in rats. Female rats were divided in 4 groups: control (C), sedentary OVX (SO), trained OVX (TO), and previously trained OVX (PTO). PTO trained four weeks previously+eight weeks after OVX and the TO group trained only after OVX on a motor treadmill. Autonomic modulation were evaluated and the adipose tissues (WAT) were removed, weighed and lipolysis was assessed. Citrate synthase activity was analysed in the soleus muscle. The trained groups prevented the impairment of BRS in relation to SO; however, only PTO reduced the low frequency band of pulse interval compared to SO. PTO reduced the weight of WAT compared to the other groups; the lipolysis in PTO was similar to C. PTO had preserved muscle metabolic injury in all types of fibres analysed. In conclusion, this study suggests that exercise training should be recommended in a pre-menopausal model in order to prevent cardiometabolic and autonomic menopause-induced deleterious effects.

2.
Front Physiol ; 9: 1471, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30420811

RESUMO

The prevalence of hypertension sharply increases in menopausal women. Recent studies have demonstrated that aerobic or resistance training may help control hypertension. In this study, we report that combining aerobic and resistance training may provide an effective therapeutic approach for hypertension control, attenuating inflammation and oxidative stress in ovariectomized rats. Female Wistar and spontaneous hypertensive rats (SHR) were distributed into four groups: sedentary control (C), sedentary hypertensive (HR), sedentary hypertensive ovariectomized (HR-O), and combined trained hypertensive ovariectomized (T-HR-O). Combined exercise training was performed on a motor treadmill (aerobic training) and on a ladder adapted to rats (resistance training), in alternate days for 8 weeks. Direct arterial pressure was recorded and oxidative stress and inflammation were evaluated in cardiac and renal tissue. Ovariectomy increases increased mean arterial blood pressure, sympathetic modulation, and oxidative stress in SHR. Combining aerobic and resistance training reduced mean arterial blood pressure (12% vs. HR-O), heart rate (8% vs. HR-O), vascular sympathetic modulation (40% vs. HR-O), and improved baroreflex sensitivity. Combined training reduced cardiac inflammation (TNF and IL-6) and cardiac and renal lipoperoxidation (59% and 57%, respectively vs. HR-O). It also enhanced cardiac (71%) and renal (76%) total antioxidant capacity when compared to HR-O group. In conclusion, combining aerobic and resistance training improves mean arterial blood pressure, cardiovascular autonomic control, preventing cardiac and renal oxidative stress and inflammation in an experimental hypertension model with surgical menopause induced with ovariectomy.

3.
Sci Rep ; 8(1): 8578, 2018 06 05.
Artigo em Inglês | MEDLINE | ID: mdl-29872081

RESUMO

This study analyzes whether autonomic dysfunction precedes cardiometabolic alterations in spontaneously hypertensive rats (SHR) with fructose overload. Animals were randomly distributed into three groups: control, hypertensive and hypertensive with fructose overload. Fructose overload (100 g/L) was initiated at 30 days old, and the animals (n = 6/group/time) were evaluated after 7, 15, 30 and 60 days of fructose consumption. Fructose consumption reduced baroreflex sensitivity by day 7, and still induced a progressive reduction in baroreflex sensitivity over the time. Fructose consumption also increased TNFα and IL-6 levels in the adipose tissue and IL-1ß levels in the spleen at days 15 and 30. Fructose consumption also reduced plasmatic nitrites (day 15 and 30) and superoxide dismutase activity (day 15 and 60), but increased hydrogen peroxide (day 30 and 60), lipid peroxidation and protein oxidation (day 60). Fructose consumption increased arterial pressure at day 30 (8%) and 60 (11%). Fructose consumption also induced a late insulin resistance at day 60, but did not affect glucose levels. In conclusion, the results show that baroreflex sensitivity impairment precedes inflammatory and oxidative stress disorders, probably by inducing hemodynamic and metabolic dysfunctions observed in metabolic syndrome.


Assuntos
Barorreflexo/fisiologia , Modelos Animais de Doenças , Coração/fisiopatologia , Síndrome Metabólica/fisiopatologia , Miocárdio/metabolismo , Tecido Adiposo/efeitos dos fármacos , Tecido Adiposo/metabolismo , Animais , Barorreflexo/efeitos dos fármacos , Frutose/administração & dosagem , Frutose/farmacologia , Coração/efeitos dos fármacos , Hemodinâmica/efeitos dos fármacos , Hemodinâmica/fisiologia , Hipertensão/metabolismo , Hipertensão/fisiopatologia , Inflamação/metabolismo , Inflamação/fisiopatologia , Resistência à Insulina , Interleucina-6/metabolismo , Masculino , Síndrome Metabólica/metabolismo , Estresse Oxidativo/fisiologia , Ratos Endogâmicos SHR , Ratos Wistar , Fator de Necrose Tumoral alfa/metabolismo
4.
Exerc Immunol Rev ; 24: 36-44, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29461970

RESUMO

Acute respiratory distress syndrome (ARDS) is defined as hypoxemic respiratory failure with intense pulmonary inflammation, involving hyperactivation of endothelial cells and neutrophils. Given the anti-inflammatory effects of aerobic exercise (AE), this study investigated whether AE performed daily for 5 weeks would inhibit extra-pulmonary LPS-induced ARDS. C57Bl/6 mice were distributed into Control, Exercise, LPS and Exercise+LPS groups. AE was performed on a treadmill for 5x/week for four weeks before LPS administration. 24hours after the final AE physical test, animals received 100ug of LPS intra-peritoneally. In addition, whole blood cell culture, neutrophils and human endothelial cells were preincubated with IL-10, an anti-inflammatory cytokine induced by exercise. AE reduced total protein levels (p<0.01) and neutrophil accumulation in bronchoalveolar lavage (BAL) (p<0.01) and lung parenchyma (p<0.01). AE reduced BAL inflammatory cytokines IL-1ß, IL-6 and GM-CSF (p<0.001), CXCL1/KC, IL-17, TNF-alpha and IGF-1 (p<0.01). Systemically, AE reduced IL-1ß, IL-6 and IFN-gamma (p<0.001), CXCL1/KC (p<0.01) and TNF-alpha (p<0.05). AE increased IL-10 levels in serum (p<0.001) and BAL (p<0.001). Furthermore, AE increased superoxide dismutase SOD (p<0.01) and decreased superoxide anion accumulation in the lungs (p<0.01). Lastly, pre-incubation with IL-10 significantly reduced LPS-induced activation of whole blood cells, neutrophils and HUVECs, as observed by reduced production of IL-1ß, IL-6, IL-8 and TNF-alpha. Our data suggest that AE inhibited LPS-induced lung inflammation by attenuating inflammatory cytokines and oxidative stress markers in mice and human cell culture via enhanced IL-10 production.


Assuntos
Interleucina-10/imunologia , Estresse Oxidativo , Condicionamento Físico Animal , Pneumonia/imunologia , Síndrome do Desconforto Respiratório/imunologia , Lesão Pulmonar Aguda , Animais , Líquido da Lavagem Broncoalveolar/citologia , Líquido da Lavagem Broncoalveolar/imunologia , Citocinas/sangue , Citocinas/imunologia , Células Endoteliais da Veia Umbilical Humana , Humanos , Interleucina-10/farmacologia , Lipopolissacarídeos , Pulmão/imunologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Neutrófilos/imunologia , Pneumonia/induzido quimicamente , Síndrome do Desconforto Respiratório/induzido quimicamente
5.
Sci Rep ; 7(1): 13687, 2017 10 20.
Artigo em Inglês | MEDLINE | ID: mdl-29057895

RESUMO

We previously reported that cholinergic stimulation with pyridostigmine (PY) induces anti-inflammatory cell recruitment soon after myocardial infarction (MI). In this study, we evaluated the anti-inflammatory effects of PY during the proliferative phase of cardiac repair by analyzing the infiltration of macrophages, Treg lymphocytes, oxidative stress and inflammatory cytokines. Wistar rats underwent control sham surgery or ligation of the left coronary artery and were randomly allocated to remain untreated (untreated infarcted group, I) or to receive PY (30 mg·kg(-1)·day(-1)) in the supplied water (infarcted treated group, I + PY). Blood pressure and heart rate variability were registered at day 5 post-MI. The animals were euthanized 7 days after thoracotomy, when the hearts were removed and processed for immunohistochemistry (CD68, CD206, FOXP3), cytokines (IL-1ß, IL-6, IL-10, TNF-α) and oxidative stress (superoxide dismutase, catalase, glutathione peroxidase, lipidic and protein peroxidation). PY treatment increased parasympathetic modulation, M2 macrophages and the anti-oxidant enzyme activity but reduced protein oxidation (carbonyls) and the concentration of IL-1ß, IL-6, TNF-α and IL-10. Cholinergic stimulation induces parasympathetic neuro-immune modulation and anti-inflammatory cell enrollment as well as prevents oxidative stress and cytokine production after MI.


Assuntos
Cardiotônicos/farmacologia , Inibidores da Colinesterase/farmacologia , Inflamação/tratamento farmacológico , Infarto do Miocárdio/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Brometo de Piridostigmina/farmacologia , Animais , Anti-Inflamatórios não Esteroides/farmacologia , Antioxidantes/farmacologia , Citocinas/metabolismo , Modelos Animais de Doenças , Hemodinâmica/efeitos dos fármacos , Inflamação/metabolismo , Inflamação/patologia , Masculino , Infarto do Miocárdio/metabolismo , Infarto do Miocárdio/patologia , Estresse Oxidativo/fisiologia , Distribuição Aleatória , Ratos Wistar
6.
Cardiovasc Diabetol ; 14: 149, 2015 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-26553117

RESUMO

BACKGROUND: The effects of streptozotocin (STZ)-induced diabetes on heart metabolism and function after myocardial infarction (MI) remodelling were investigated in rats. METHODS: Fifteen days after STZ (50 mg/kg b.w. i.v.) injection, MI was induced by surgical occlusion of the left coronary artery. Two weeks after MI induction, contents of glycogen, ATP, free fatty acids and triacylglycerols (TG) and enzyme activities of glycolysis and Krebs cycle (hexokinase, glucose-6-phosphate dehydrogenase, phosphofructokinase, citrate synthase) and expression of carnitine palmitoyl-CoA transferase I (a key enzyme of mitochondrial fatty acid oxidation) were measured in the left ventricle (LV). Plasma glucose, free fatty acids and triacylglycerol levels were determined. Ejection fraction (EF) and shortening fraction (SF) were also measured by echocardiography. RESULTS: Glycogen and TG contents were increased (p < 0.05) whereas ATP content was decreased in the LV of the non-infarcted diabetic group when compared to the control group (p < 0.05). When compared to infarcted control rats (MI), the diabetic infarcted rats (DI) showed (p < 0.05): increased plasma glucose and TG levels, elevated free fatty acid levels and increased activity of, citrate synthase and decreased ATP levels in the LV. Infarct size was smaller in the DI group when compared to MI rats (p < 0.05), and this was associated with higher EF and SF (p < 0.05). CONCLUSIONS: Systolic function was preserved or recovered more efficiently in the heart from diabetic rats two weeks after MI, possibly due to the high provision of glucose and free fatty acids from both plasma and heart glycogen and triacylglycerol stores.


Assuntos
Glicemia/metabolismo , Diabetes Mellitus Experimental/sangue , Metabolismo Energético , Ácidos Graxos/sangue , Infarto do Miocárdio/sangue , Miocárdio/metabolismo , Função Ventricular Esquerda , Remodelação Ventricular , Trifosfato de Adenosina/metabolismo , Animais , Carnitina O-Palmitoiltransferase/metabolismo , Ciclo do Ácido Cítrico , Diabetes Mellitus Experimental/complicações , Glicogênio/metabolismo , Glicólise , Masculino , Infarto do Miocárdio/complicações , Infarto do Miocárdio/patologia , Infarto do Miocárdio/fisiopatologia , Miocárdio/patologia , Ratos Wistar , Espécies Reativas de Oxigênio/metabolismo , Volume Sistólico , Sístole , Fatores de Tempo , Triglicerídeos/sangue
7.
Am J Physiol Regul Integr Comp Physiol ; 309(12): R1532-9, 2015 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-26423710

RESUMO

It is now well established that after menopause cardiometabolic disorders become more common. Recently, resistance exercise has been recommended as a complement to aerobic (combined training, CT) for the treatment of cardiometabolic diseases. The aim of this study was to evaluate the effects of CT in hypertensive ovariectomized rats undergoing fructose overload in blood pressure variability (BPV), inflammation, and oxidative stress parameters. Female rats were divided into the following groups (n = 8/group): sedentary normotensive Wistar rats (C), and sedentary (FHO) or trained (FHOT) ovariectomized spontaneously hypertensive rats undergoing and fructose overload. CT was performed on a treadmill and ladder adapted to rats in alternate days (8 wk; 40-60% maximal capacity). Arterial pressure (AP) was directly measured. Oxidative stress and inflammation were measured on cardiac and renal tissues. The association of risk factors (hypertension + ovariectomy + fructose) promoted increase in insulin resistance, mean AP (FHO: 174 ± 4 vs. C: 108 ± 1 mmHg), heart rate (FHO: 403 ± 12 vs. C: 352 ± 11 beats/min), BPV, cardiac inflammation (tumor necrosis factor-α-FHO: 65.8 ± 9.9 vs. C: 23.3 ± 4.3 pg/mg protein), and oxidative stress cardiac and renal tissues. However, CT was able to reduce mean AP (FHOT: 158 ± 4 mmHg), heart rate (FHOT: 303 ± 5 beats/min), insulin resistance, and sympathetic modulation. Moreover, the trained rats presented increased nitric oxide bioavailability, reduced tumor necrosis factor-α (FHOT: 33.1 ± 4.9 pg/mg protein), increased IL-10 in cardiac tissue and reduced lipoperoxidation, and increased antioxidant defenses in cardiac and renal tissues. In conclusion, the association of risk factors promoted an additional impairment in metabolic, cardiovascular, autonomic, inflammatory, and oxidative stress parameters and combined exercise training was able to attenuate these dysfunctions.


Assuntos
Sistema Nervoso Autônomo/fisiopatologia , Hipertensão/terapia , Inflamação/terapia , Menopausa , Síndrome Metabólica/terapia , Estresse Oxidativo , Treinamento Resistido , Animais , Pressão Arterial , Sistema Nervoso Autônomo/metabolismo , Biomarcadores/sangue , Modelos Animais de Doenças , Feminino , Frutose , Frequência Cardíaca , Hipertensão/sangue , Hipertensão/fisiopatologia , Inflamação/sangue , Inflamação/fisiopatologia , Mediadores da Inflamação/sangue , Resistência à Insulina , Rim/metabolismo , Peroxidação de Lipídeos , Menopausa/sangue , Síndrome Metabólica/sangue , Síndrome Metabólica/fisiopatologia , Miocárdio/metabolismo , Ovariectomia , Ratos Endogâmicos SHR , Ratos Wistar , Comportamento Sedentário , Fatores de Tempo
8.
Biomed Res Int ; 2015: 496378, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25893195

RESUMO

RC-3095, a selective GRPR antagonist, has been shown to have anti-inflammatory properties in different models of inflammation. However, its protective effect on lungs submitted to lung ischemia-reperfusion injury has not been addressed before. Then, we administrated RC-3095 intravenously before and after lung reperfusion using an animal model of lung ischemia-reperfusion injury (LIRI) by clamping the pulmonary hilum. Twenty Wistar rats were subjected to an experimental model in four groups: SHAM, ischemia-reperfusion (IR), RC-Pre, and RC-Post. The final mean arterial pressure significantly decreased in IR and RC-Pre compared to their values before reperfusion (P < 0.001). The RC-Post group showed significant decrease of partial pressure of arterial oxygen at the end of the observation when compared to baseline (P = 0.005). Caspase-9 activity was significantly higher in the RC-Post as compared to the other groups (P < 0.013). No significant differences were observed in eNOS activity among the groups. The groups RC-Pre and RC-Post did not show any significant decrease in IL-1ß (P = 0.159) and TNF-α (P = 0.260), as compared to IR. The histological score showed no significant differences among the groups. In conclusion, RC-3095 does not demonstrate a protective effect in our LIRI model. Additionally, its use after reperfusion seems to potentiate cell damage, stimulating apoptosis.


Assuntos
Antineoplásicos/farmacologia , Bombesina/análogos & derivados , Pneumopatias/metabolismo , Pulmão/metabolismo , Fragmentos de Peptídeos/farmacologia , Receptores da Bombesina/antagonistas & inibidores , Traumatismo por Reperfusão/metabolismo , Animais , Bombesina/farmacologia , Modelos Animais de Doenças , Interleucina-1beta/metabolismo , Pulmão/patologia , Pneumopatias/tratamento farmacológico , Pneumopatias/patologia , Masculino , Óxido Nítrico Sintase Tipo III/metabolismo , Ratos , Ratos Wistar , Receptores da Bombesina/metabolismo , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/patologia , Fator de Necrose Tumoral alfa/metabolismo
9.
BMC Cardiovasc Disord ; 14: 185, 2014 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-25495455

RESUMO

BACKGROUND: Metabolic syndrome is characterized by the association of 3 or more risk factors, including: abdominal obesity associated with an excess of abdominal fat, insulin resistance, type 2 diabetes, dyslipidemia and hypertension. Moreover, the prevalence of hypertension and metabolic dysfunctions sharply increases after the menopause. However, the mechanisms involved in these changes are not well understood. Thus, the aim of this study was to assess the effects of fructose overload on cardiovascular autonomic modulation, inflammation and cardiac oxidative stress in an experimental model of hypertension and menopause. METHODS: Female SHR rats were divided into (n = 8/group): hypertensive (H), hypertensive ovariectomized (HO) and hypertensive ovariectomized undergoing fructose overload (100 g/L in drinking water) (FHO). Arterial pressure (AP) signals were directly recorded. Cardiac autonomic modulation was evaluated by spectral analysis. Oxidative stress was evaluated in cardiac tissue. RESULTS: AP was higher in the FHO group when compared to the other groups. Fructose overload promoted an increase in body and fat weight, triglyceride concentration and a reduction in insulin sensitivity. IL-10 was reduced in the FHO group when compared to the H group. TNF-α was higher in the FHO when compared to all other groups. Lipoperoxidation was higher and glutathione redox balance was reduced in the FHO group when compared to other groups, an indication of increased oxidative stress. A negative correlation was found between IL-10 and adipose tissue. CONCLUSION: Fructose overload promoted an impairment in cardiac autonomic modulation associated with inflammation and oxidative stress in hypertensive rats undergoing ovarian hormone deprivation.


Assuntos
Sistema Nervoso Autônomo/fisiopatologia , Coração/inervação , Hipertensão/fisiopatologia , Menopausa/fisiologia , Síndrome Metabólica/fisiopatologia , Estresse Oxidativo/fisiologia , Adiposidade , Animais , Biomarcadores/sangue , Glicemia/metabolismo , Peso Corporal , Modelos Animais de Doenças , Feminino , Frutose , Hemodinâmica , Inflamação/fisiopatologia , Síndrome Metabólica/induzido quimicamente , Ratos Endogâmicos SHR , Triglicerídeos/sangue
10.
Cardiovasc Diabetol ; 13: 131, 2014 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-25301475

RESUMO

BACKGROUND: Previous research has demonstrated that hyperglycemia may protect the heart against ischemic injury. The aim of the present study was to investigate the association between hyperglycemia and myocardial infarction on cardiovascular autonomic modulation and cardiac oxidative stress profile in rats. Male Wistar rats were divided into: control (C), diabetic (D), myocardial infarcted (MI) and diabetic infarcted rats (DMI). METHODS: Diabetes was induced by streptozotocin (STZ, 50 mg/Kg) at the beginning of the protocol and MI was induced by left coronary occlusion 15 days after STZ. Thirty days after streptozocin-induced diabetes, cardiovascular autonomic modulation was evaluated by spectral analysis, and oxidative stress profile was determined by antioxidant enzyme activities and superoxide anion, together with protein carbonylation and redox balance of glutathione (GSH/GSSG). RESULTS: The diabetic and infarcted groups showed decreased heart rate variability and vagal modulation (p < 0.05); however, sympathetic modulation decreased only in diabetic groups (p < 0.05). Sympatho/vagal balance and vascular sympathetic modulation were increased only in the MI group (p < 0.05). Diabetes promoted an increase in catalase concentration (p < 0.05). Glutathione peroxidase activity was increased only in DMI when compared to the other groups (p < 0.05). Superoxide anion and protein carbonylation were increased only in MI group (p < 0.05). Cardiac redox balance, as evaluated by GSH/GSSG, was lower in the MI group (p < 0.05). CONCLUSIONS: These data suggest that hyperglycemia promotes compensatory mechanisms that may offer protection against ischemia, as demonstrated by increased antioxidants, decreased pro-oxidants and protein damage, possibly related to the improvements in both redox balance and sympathetic modulation to the heart.


Assuntos
Diabetes Mellitus Experimental/metabolismo , Hiperglicemia/metabolismo , Infarto do Miocárdio/metabolismo , Estresse Oxidativo , Animais , Antioxidantes/farmacologia , Diabetes Mellitus Experimental/induzido quimicamente , Glutationa/metabolismo , Masculino , Infarto do Miocárdio/fisiopatologia , Estresse Oxidativo/efeitos dos fármacos , Ratos Wistar , Espécies Reativas de Oxigênio/metabolismo , Estreptozocina
11.
World J Cardiol ; 6(6): 449-54, 2014 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-24976917

RESUMO

While clinical data have suggested that the diabetic heart is more susceptible to ischemic heart disease (IHD), animal data have so far pointed to a lower probability of IHD. Thus, the aim of this present review is to look at these conflicting results and discuss the protective mechanisms that conditioned hyperglycemia may confer to the heart against ischemic injury. Several mechanisms have been proposed to explain the cardioprotective action of high glucose exposure, namely, up-regulation of anti-apoptotic factor Bcl-2, inactivation of pro-apoptotic factor bad, and activation of pro-survival factors such as protein kinase B (Akt), vascular endothelial growth factor (VEGF), hypoxia inducible factor-1α and protein kinase C-ε. Indeed, cytosolic increase in Ca(2+) concentration, the mitochondrial permeability transition pore, plays a key role in the genesis of ischemic injury. Previous studies have shown that the diabetic heart decreased Na(+)/Ca(2+) and Na(+)/H(+) exchanger activity and as such it accumulates less Ca(2+) in cardiomyocyte, thus preventing cardiac injury and the associated heart dysfunctions. In addition, the expression of VEGF in diabetic animals leads to increased capillary density before myocardial infarction. Despite poor prognostic in the long-term, all these results suggest that diabetes mellitus and consequently hyperglycemia may indeed play a cardioprotective role against myocardial infarction in the short term.

12.
J Card Fail ; 18(9): 734-44, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22939043

RESUMO

BACKGROUND: Exercise training (ET) has been used as a nonpharmacological strategy for treatment of diabetes and myocardial infarction (MI) separately. We evaluated the effects ET on functional and molecular left ventricular (LV) parameters as well as on autonomic function and mortality in diabetics after MI. METHODS AND RESULTS: Male Wistar rats were divided into control (C), sedentary-diabetic infarcted (SDI), and trained-diabetic infarcted (TDI) groups. MI was induced after 15 days of streptozotocin-diabetes induction. Seven days after MI, the trained group underwent ET protocol (90 days, 50-70% maximal oxygen consumption-VO(2)max). LV function was evaluated noninvasively and invasively; baroreflex sensitivity, pulse interval variability, cardiac output, tissue blood flows, VEGF mRNA and protein, HIF1-α mRNA, and Ca(2+) handling proteins were measured. MI area was reduced in TDI (21 ± 4%) compared with SDI (38 ± 4%). ET induced improvement in cardiac function, hemodynamics, and tissue blood flows. These changes were probable consequences of a better expression of Ca(2+) handling proteins, increased VEGF mRNA and protein expression as well as improvement in autonomic function, that resulted in reduction of mortality in TDI (33%) compared with SDI (68%) animals. CONCLUSIONS: ET reduced cardiac and peripheral dysfunction and preserved autonomic control in diabetic infarcted rats. Consequently, these changes resulted in improved VO(2)max and survival after MI.


Assuntos
Sistema Nervoso Autônomo , Circulação Coronária , Coração/fisiopatologia , Infarto do Miocárdio/patologia , Condicionamento Físico Animal , Análise de Variância , Animais , Cálcio/metabolismo , Débito Cardíaco , Hemodinâmica , Masculino , Infarto do Miocárdio/diagnóstico por imagem , Infarto do Miocárdio/prevenção & controle , Consumo de Oxigênio , Ratos , Ratos Wistar , Fatores de Tempo , Ultrassonografia , Fator A de Crescimento do Endotélio Vascular
13.
J Cardiovasc Pharmacol ; 59(1): 58-65, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21921804

RESUMO

Activation of renin-angiotensin system has been linked to cardiovascular and autonomic dysfunctions in diabetes. Experiments were performed to investigate the effects of angiotensin-converting enzyme inhibitor (ACEI), enalapril, on cardiac and autonomic functions in diabetic rats. Diabetes was induced by streptozotocin (50 mg/kg), and rats were treated with enalapril (1 mg · kg(-1) · d(-1)). After 30 days, evaluations were performed in control, diabetic, and enalapril-treated groups. Cardiac function was evaluated by echocardiography and through cannulation of the left ventricle (at baseline and in response to volume overload). Heart rate and systolic blood pressure variabilities were evaluated in the time and frequency domains. Streptozotocin rats had left ventricular systolic and diastolic dysfunctions, expressed by reduced ejection fraction and increased isovolumic relaxation time. The ACEI prevented these changes, improved diastolic cardiac responses to volume overload and total power of heart rate variability, reduced the ACE1 activity and protein expression and cardiac angiotensin (Ang) II levels, and increased angiotensin-converting enzyme 2 activity, despite unchanged blood pressure. Correlations were obtained between Ang II content with systolic and diastolic functions and heart rate variability. These findings provide evidence that the low-dose ACEI prevents autonomic and cardiac dysfunctions induced by diabetes without changing blood pressure and associated with reduced cardiac Ang II and increased angiotensin-converting enzyme 2 activity.


Assuntos
Angiotensina II/metabolismo , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Sistema Nervoso Autônomo/efeitos dos fármacos , Diabetes Mellitus Experimental/tratamento farmacológico , Enalapril/uso terapêutico , Coração/efeitos dos fármacos , Enzima de Conversão de Angiotensina 2 , Inibidores da Enzima Conversora de Angiotensina/administração & dosagem , Animais , Sistema Nervoso Autônomo/fisiopatologia , Glicemia/análise , Pressão Sanguínea/efeitos dos fármacos , Western Blotting , Peso Corporal/efeitos dos fármacos , Cromatografia Líquida de Alta Pressão , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/fisiopatologia , Relação Dose-Resposta a Droga , Eletrocardiografia , Enalapril/administração & dosagem , Coração/fisiopatologia , Frequência Cardíaca/efeitos dos fármacos , Masculino , Miocárdio/enzimologia , Peptidil Dipeptidase A/metabolismo , Ratos , Ratos Wistar , Sistema Renina-Angiotensina/efeitos dos fármacos , Função Ventricular Esquerda/efeitos dos fármacos
14.
Eur Heart J ; 32(7): 904-12, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20675661

RESUMO

AIMS: To test the effects of early exercise training (ET) on left ventricular (LV) and autonomic functions, haemodynamics, tissues blood flows (BFs), maximal oxygen consumption (VO(2) max), and mortality after myocardial infarction (MI) in rats. METHODS AND RESULTS: Male Wistar rats were divided into: control (C), sedentary-infarcted (SI), and trained-infarcted (TI). One week after MI, TI group underwent an ET protocol (90 days, 50-70% VO(2) max). Left ventricular function was evaluated non-invasively and invasively. Baroreflex sensitivity, heart rate variability, and pulse interval were measured. Cardiac output (CO) and regional BFs were determined using coloured microspheres. Infarcted area was reduced in TI (19 ± 6%) compared with SI (34 ± 5%) after ET. Exercise training improved the LV and autonomic functions, the CO and regional BF changes induced by MI, as well as increased SERCA2 expression and mRNA vascular endothelial growth factor levels. These changes brought about by ET resulted in mortality rate reduction in the TI (13%) group compared with the SI (54%) group. CONCLUSION: Early aerobic ET reduced cardiac and peripheral dysfunctions and preserved cardiovascular autonomic control after MI in trained rats. Consequently, these ET-induced changes resulted in improved functional capacity and survival after MI.


Assuntos
Doenças do Sistema Nervoso Autônomo/fisiopatologia , Infarto do Miocárdio/fisiopatologia , Condicionamento Físico Animal , Animais , Barorreflexo/fisiologia , Peso Corporal , Débito Cardíaco/fisiologia , Ecocardiografia , Frequência Cardíaca/fisiologia , Estimativa de Kaplan-Meier , Masculino , Microesferas , Infarto do Miocárdio/mortalidade , Consumo de Oxigênio/fisiologia , Ratos , Ratos Wistar , Fluxo Sanguíneo Regional/fisiologia , ATPases Transportadoras de Cálcio do Retículo Sarcoplasmático/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Disfunção Ventricular Esquerda/fisiopatologia
15.
Eur J Heart Fail ; 12(7): 659-67, 2010 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-20406798

RESUMO

AIMS: Exposure to a high glucose medium or diabetes has been found to protect the heart against ischaemia. The activation of antiapoptotic and proliferative factors seems to be involved in this cardioprotection. This study was designed to evaluate the role of hyperglycaemia in cardiac function, programmed cell survival, and cell death in diabetic rats after myocardial infarction (MI). METHODS AND RESULTS: Male Wistar rats were divided into four groups (n = 8): control (C), diabetic (D), myocardial infarcted (MI), and diabetic myocardial infarcted (DI). The following measures were assessed in the left ventricle: size of MI, systolic and diastolic function by echocardiography, cytokines by ELISA (TNF-alpha, IL-1beta, IL-6, and IL-10), gene expression by real-time PCR (Bax, Fas, p53, Bcl-2, HIF1-alpha, VEGF, and IL8r), caspase-3 activity by spectrofluorometric assay, glucose transporter type 1 and 4 (GLUT-1 and GLUT-4) protein expression by western blotting, and capillary density and fibrosis by histological analysis. Systolic function was improved by hyperglycaemia in the DI group, and this was accompanied by no improvement in diastolic dysfunction, a reduction of 36% in MI size, reduced proinflammatory cytokines, apoptosis activation, and an increase in cell survival factors (HIF1-alpha, VEGFa and IL8r) assessed 15 days post-MI. Moreover, hyperglycaemia resulted in angiogenesis (increased capillary density) before and after MI, accompanied by a reduction in fibrosis. CONCLUSION: Together, these results suggest that greater plasticity and cellular resistance to ischaemic injury result from chronic diabetic hyperglycaemia in rat hearts.


Assuntos
Diabetes Mellitus Experimental/fisiopatologia , Coração/fisiopatologia , Hiperglicemia/fisiopatologia , Infarto do Miocárdio/fisiopatologia , Miócitos Cardíacos/fisiologia , Animais , Apoptose/fisiologia , Caspase 3/metabolismo , Sobrevivência Celular/fisiologia , Citocinas/análise , Proteínas Facilitadoras de Transporte de Glucose/metabolismo , Masculino , Ratos , Fator de Necrose Tumoral alfa/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo
16.
São Paulo; s.n; 2009. [113] p. graf, tab, ilus.
Tese em Português | LILACS | ID: lil-554436

RESUMO

Estudos mostram que a exposição ao meio hiperglicêmico ou diabetes protege o coração contra insultos patológicos, incluindo isquemia. A ativação de fatores anti-apoptóticos e proliferativos parece estar envolvida com esta cardioproteção. Este estudo foi desenhado para investigar a modulação da viabilidade de fibroblastos cardíacos submetidos à hipóxia tratados previamente com meio hiperglicêmico, e os efeitos de 15 dias de infarto do miocárdio (IM) na função ventricular em ratos diabéticos sobre os fatores de morte e sobrevida celular. Foram utilizados ratos Wistar machos e as análises foram realizadas no ventrículo esquerdo. Para as análises in vitro, os fibroblastos cardíacos foram obtidos por digestão enzimática (tripsina/colagenase), e cultivados em dois meios: baixa Glicose (5mM) e alta Glicose (25mM análogo ao plasma diabético). As células confluentes (80%) foram submetidas à hipóxia por incubadora modular com gás (5,6% de CO2 e 94,4% de N2); após as células foram mantidas em estufa a 37ºC por 6; 12; 24; 48 e 72hs. Experimentos de citometria de fluxo foram realizados para análise da viabilidade celular e fragmentação de DNA, ambas para verificação de apoptose e confirmadas pelas medidas de AnexinaV/FITC/IP. A expressão do fator de crescimento endotelial vascular (VEGF) foi medida no sobrenadante dos meios por ELISA. Para as análises in vivo, os ratos foram divididos (N=8/grupo) em grupos: controle (C), diabético (D), infartado (I) e diabético infartado (DI). Quinze dias após a indução do diabetes ou não, com injeção de estroptozotocina (50mg/Kg) ou tampão citrato, os grupos I e DI foram submetidos à ligadura da artéria coronária. Após 15 dias de IM e/ou 30 de diabetes, a função cardíaca (sistólica e diastólica) foi analisada por ecocardiograma, além da avaliação do tamanho do IM em 24 horas e 15 dias. As citocinas inflamatórias foram medidas por ELISA, a expressão gênica dos fatores de morte e sobrevida celular foram avaliados por PCR...


Studies showed that exposure to hyperglycemia or diabetes protects the heart against pathological insults, including ischemia. The activation of anti-apoptotic factors and proliferation seem to be involved in this cardioprotection. This study was designed to investigate the feasibility of modulation of hyperglycemic-environment pretreated-cardiac fibroblasts subjected to hypoxia, and the effects of 15 days of myocardial infarction on ventricular function in diabetic rats and on the causes of death and cell survival. Male Wistar rats were used and the analyses were performed in the left ventricle. For in vitro experiments, cardiac fibroblasts were obtained by enzymatic digestion (trypsin/collagenase) and they were cultivated in two different mediums: Low Glucose (5mM) and High Glucose (25mM similar to diabetic plasma). Confluent cells (80%) were subjected to hypoxia by modular incubator with gas (5.6% CO2 and 94.4% N2) at 37 ° C for 6, 12, 24, 48 and 72h. Flow cytometry was employed to the analysis of cell viability and DNA fragmentation, both for verification of apoptosis process and confirmed by AnexinaV / FITC / IP. The expression of vascular growth factor (VEGF) was measured in the supernatant medium by ELISA. For in vivo experiments, the rats were divided (N = 8/group) in control (C), diabetic (D), infarcted (I) and diabetic infarcted (DI) groups. After 15 days of induction of diabetes by estreptozotocin (50mg/kg) or citrate buffer, the I and DI groups underwent coronary artery ligation. After 15 days of myocardium infarction (MI) and/or 30 of diabetes, cardiac function (systolic and diastolic) was analyzed by echocardiogram, as well as the size of infarction at both, 24 hours and 15 days. The inflammatory cytokines were measured by ELISA, the gene expression of factors for death and cell survival by real-time PCR, the activity of caspase 3 by spectrofluorimetry, the protein expression of glucose transporters (GLUT)...


Assuntos
Animais , Ratos , Apoptose , Glicemia , Hipóxia Celular , Citocinas , Fibroblastos , Fibrose , Hiperglicemia , Infarto do Miocárdio
17.
Clin Exp Pharmacol Physiol ; 35(2): 113-9, 2008 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-17973933

RESUMO

1. Heart regeneration after myocardial infarction (MI) can occur after cell therapy, but the mechanisms, cell types and delivery methods responsible for this improvement are still under investigation. In the present study, we evaluated the impact of systemic delivery of bone marrow cells (BMC) and cultivated mesenchymal stem cells (MSC) on cardiac morphology, function and mortality in spontaneously hypertensive rats (SHR) submitted to coronary occlusion. 2. Female syngeneic adult SHR, submitted or not (control group; C) to MI, were treated with intravenous injection of MSC (MI + MSC) or BMC (MI + BM) from male rats and evaluated after 1, 15 and 30 days by echocardiography. Systolic blood pressure (SBP), functional capacity, histology, mortality rate and polymerase chain reaction for the Y chromosome were also analysed. 3. Myocardial infarction induced a decrease in SBP and BMC, but not MSC, prevented this decrease. An improvement in functional capacity and ejection fraction (38 +/- 4, 39 +/- 3 and 58 +/- 2% for MI, MI + MSC and MI + BM, respectively; P < 0.05), as well as a reduction of the left ventricle infarcted area, were observed in rats from the MI + BM group compared with the other three groups. Treated animals had a significantly reduced lesion tissue score. The mortality rate in the C, MI + BM, MI + MSC and MI groups was 0, 0, 16.7 and 44.4%, respectively (P < 0.05 for the MI + MSC and MI groups compared with the C and MI + BM groups). 4. The results of the present study suggest that systemic administration of BMC can improve left ventricular function, functional capacity and, consequently, reduce mortality in an animal model of MI associated with hypertension. We speculate that the cells transiently home to the myocardium, releasing paracrine factors that recruit host cells to repair the lesion.


Assuntos
Células-Tronco Adultas/transplante , Transplante de Medula Óssea , Hipertensão/cirurgia , Transplante de Células-Tronco Mesenquimais , Infarto do Miocárdio/cirurgia , Função Ventricular Esquerda , Remodelação Ventricular , Células-Tronco Adultas/metabolismo , Animais , Pressão Sanguínea , Movimento Celular , Células Cultivadas , Vasos Coronários/cirurgia , Modelos Animais de Doenças , Feminino , Hipertensão/complicações , Hipertensão/diagnóstico por imagem , Hipertensão/fisiopatologia , Ligadura , Masculino , Infarto do Miocárdio/complicações , Infarto do Miocárdio/diagnóstico por imagem , Infarto do Miocárdio/fisiopatologia , Miocárdio/metabolismo , Ratos , Ratos Endogâmicos SHR , Regeneração , Volume Sistólico , Fatores de Tempo , Ultrassonografia , Cromossomo Y/metabolismo
18.
Arq Bras Endocrinol Metabol ; 51(2): 185-94, 2007 Mar.
Artigo em Português | MEDLINE | ID: mdl-17505625

RESUMO

Much new information has been published in the last few years regarding pathophysiology of cardiovascular autonomic dysfunction in diabetic rats and mice. Our group has been studying the time-course cardiovascular changes associated with experimental diabetes in the last years, and obtained consistent evidences of severe dysautonomia in diabetes animal models. The aim of this manuscript is to review the contribution that studies involving different animal models of insulin deficiency or resistance have given to understand, treat and prevent diabetic cardiovascular autonomic dysfunction.


Assuntos
Doenças do Sistema Nervoso Autônomo/fisiopatologia , Sistema Cardiovascular/fisiopatologia , Diabetes Mellitus Experimental/fisiopatologia , Neuropatias Diabéticas/fisiopatologia , Animais , Intolerância à Glucose/fisiopatologia , Insulina/deficiência , Resistência à Insulina/fisiologia , Camundongos , Ratos , Estreptozocina
19.
Cardiovasc Diabetol ; 6: 14, 2007 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-17462095

RESUMO

BACKGROUND: Because cardiomyopathy is the leading cause of death in diabetic patients, the determination of myocardial function in diabetes mellitus is essential. In the present study, we provide an integrated approach, using noninvasive echocardiography and invasive hemodynamics to assess early changes in myocardial function of diabetic rats. METHODS: Diabetes was induced by streptozotocin injection (STZ, 50 mg/kg). After 30 days, echocardiography (noninvasive) at rest and invasive left ventricular (LV) cannulation at rest, during and after volume overload, were performed in diabetic (D, N = 7) and control rats (C, N = 7). The Student t test was performed to compare metabolic and echocardiographic differences between groups at 30 days. ANOVA was used to compare LV invasive measurements, followed by the Student-Newman-Keuls test. Differences were considered significant at P < 0.05 for all tests. RESULTS: Diabetes impaired LV systolic function expressed by reduced fractional shortening, ejection fraction, and velocity of circumferential fiber shortening compared with that in the control group. The diabetic LV diastolic dysfunction was evidenced by diminished E-waves and increased A-waves and isovolumic relaxation time. The myocardial performance index was greater in diabetic compared with control rats, indicating impairment in diastolic and systolic function. The LV systolic pressure was reduced and the LV end-diastolic pressure was increased at rest in diabetic rats. The volume overload increased LVEDP in both groups, while LVEDP remained increased after volume overload only in diabetic rats. CONCLUSION: These results suggest that STZ-diabetes induces systolic and diastolic dysfunction at rest, and reduces the capacity for cardiac adjustment to volume overload. In addition, it was also demonstrated that rodent echocardiography can be a useful, clinically relevant tool for the study of initial diabetic cardiomyopathy manifestations in asymptomatic patients.


Assuntos
Cateterismo Cardíaco , Cardiomiopatias/diagnóstico por imagem , Diabetes Mellitus Experimental/complicações , Ecocardiografia , Disfunção Ventricular Esquerda/diagnóstico por imagem , Animais , Cardiomiopatias/metabolismo , Cardiomiopatias/fisiopatologia , Diástole , Modelos Animais de Doenças , Hiperglicemia/complicações , Masculino , Ratos , Ratos Wistar , Volume Sistólico , Disfunção Ventricular Esquerda/metabolismo , Disfunção Ventricular Esquerda/fisiopatologia , Pressão Ventricular
20.
Arq. bras. endocrinol. metab ; 51(2): 185-194, mar. 2007.
Artigo em Português | LILACS | ID: lil-449572

RESUMO

Muitas informações novas têm sido publicadas nos últimos anos a respeito da fisiopatologia da disfunção autonômica cardiovascular em ratos e camundongos diabéticos. Nosso grupo tem estudado o curso temporal das alterações cardiovasculares associadas ao diabetes experimental há alguns anos, obtendo evidências consistentes de grave disautonomia em modelos animais de diabetes. O objetivo deste trabalho foi revisar a contribuição que estudos envolvendo diferentes modelos de deficiência e resistência à insulina têm fornecido para o entendimento, tratamento e prevenção da disfunção autonômica cardiovascular do diabetes.


Much new information has been published in the last few years regarding pathophysiology of cardiovascular autonomic dysfunction in diabetic rats and mice. Our group has been studying the time-course cardiovascular changes associated with experimental diabetes in the last years, and obtained consistent evidences of severe dysautonomia in diabetes animal models. The aim of this manuscript is to review the contribution that studies involving different animal models of insulin deficiency or resistance have given to understand, treat and prevent diabetic cardiovascular autonomic dysfunction.


Assuntos
Animais , Camundongos , Ratos , Doenças do Sistema Nervoso Autônomo/fisiopatologia , Sistema Cardiovascular/fisiopatologia , Diabetes Mellitus Experimental/fisiopatologia , Neuropatias Diabéticas/fisiopatologia , Intolerância à Glucose/fisiopatologia , Resistência à Insulina/fisiologia , Insulina/deficiência , Estreptozocina
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