Ana Paula Lima Leopoldo

Vascular Alterations in High-fat Diet-obese Rats: Role of Endothelial L-arginine/NO Pathway

FUNDAMENTO: Mecanismos subjacentes a anormalidades vasculares na obesidade ainda nao estao completamente esclarecidos. OBJETIVO: Foi avaliada a via do oxido nitrico/L-arginina na resposta vascular de ratos obesos por dieta rica em gordura, enfocando as celulas endoteliais e do musculo liso. METODOS: Ratos com 30 dias de vida foram divididos em 2 grupos: controle (C) e obeso (OB, ratos sob dieta rica em gordura por 30 semanas). Apos 30 semanas, foram registrados o peso corporal, indice de adiposidade, pressao arterial e perfis metabolicos e endocrinos dos animais. Foram obtidas curvas para noradrelanina na ausencia e presenca de inibidor de oxido nitrico sintase (L-NAME, 3x10-4M) em aorta toracica intacta e com desnudamento em ratos C e OB. RESULTADOS: As medidas de peso corporal, indice de adiposidade, leptina e insulina aumentaram nos ratos OB, enquanto a pressao arterial permaneceu inalterada. A obesidade tambem produziu tolerância a glicose e resistencia a insulina. A reatividade a noradrenalina da aorta intacta foi similar em ratos C e OB. A presenca de L-NAME produziu um aumento similar nas respostas maximas, mas um desvio maior a esquerda das respostas nas aortas intactas dos ratos C em relacao aos ratos OB [EC50 (x10-7M): C = 1,84 (0,83-4,07), O = 2,49 (1,41-4,38); presenca de L-NAME C = 0,02 (0,01-0,04)*, O = 0,21 (0,11-0,40)*†,*p < 0,05 vs controle respectivo,†p < 0,05 vs controle mais L-NAME, n = 6-7]. Nenhum dos protocolos alterou a reatividade a noradrenalina de aortas com desnudamento. CONCLUSAO: A obesidade induzida por dieta rica em gordura promove alteracoes metabolicas e vasculares. A alteracao vascular envolveu uma melhora da via endotelial L-arginina/NO provavelmente relacionada a hiperinsulinemia e hiperleptinemia induzidas por dieta. A maior resistencia aos efeitos do L-NAME na aorta de ratos obesos diz respeito a menor vulnerabilidade de individuos obesos na presenca de patologias associadas que causam danos a atividade do sistema NO.BACKGROUND Mechanisms underlying vascular abnormalities in obesity remain to be completely clarified. OBJECTIVE L-arginine/nitric oxide pathway was evaluated on vascular response of high-fat diet-obese rats, focusing on endothelial and smooth muscle cells. METHODS 30-day-old rats were divided in two groups: control (C) and obese (OB, high-fat diet for 30 weeks). After 30 weeks, body weight, adiposity index, blood pressure, and metabolic and endocrine profiles of the animals were recorded. Curves to noradrenaline were obtained in absence and presence of nitric oxide synthase inhibitor (L-NAME, 3x10-4M) on intact and denuded thoracic aorta from C and OB rats. RESULTS Body weight, adiposity index, leptin and insulin levels were increased in OB, while blood pressure was unchanged. Obesity also produced glucose tolerance and insulin resistance. Reactivity to noradrenaline of intact aorta was similar in C and OB rats. L-NAME presence produced a similar increase in maximal responses, but a higher leftward shift of noradrenaline responses in intact aorta from C than in OB rats [EC50 (x10-7M): C = 1.84 (0.83-4.07), O = 2.49 (1.41-4.38); L-NAME presence C = 0.02 (0.01-0.04)*, O = 0.21 (0.11-0.40)**p < 0.05 vs respective control, p < 0.05 vs control plus L-NAME, n = 6-7]. None of the protocols altered the reactivity to noradrenaline of denuded aortas. CONCLUSION High-fat diet-induced obesity promotes metabolic and vascular alterations. The vascular alteration involved an endothelial L-arginine/NO pathway improvement was probably correlated to diet-induced hyperinsulinemia and hyperleptinemia. The greater resistance to L-NAME effects in aorta of obese rats raises concerns about the lower cardiovascular vulnerability of obese individuals in the presence of associated pathologies that impair NO-system activity.

Alterações vasculares em ratos obesos por dieta rica em gordura: papel da Via L-arginina/NO Endotelial

FUNDAMENTO: Mecanismos subjacentes a anormalidades vasculares na obesidade ainda nao estao completamente esclarecidos. OBJETIVO: Foi avaliada a via do oxido nitrico/L-arginina na resposta vascular de ratos obesos por dieta rica em gordura, enfocando as celulas endoteliais e do musculo liso. METODOS: Ratos com 30 dias de vida foram divididos em 2 grupos: controle (C) e obeso (OB, ratos sob dieta rica em gordura por 30 semanas). Apos 30 semanas, foram registrados o peso corporal, indice de adiposidade, pressao arterial e perfis metabolicos e endocrinos dos animais. Foram obtidas curvas para noradrelanina na ausencia e presenca de inibidor de oxido nitrico sintase (L-NAME, 3x10-4M) em aorta toracica intacta e com desnudamento em ratos C e OB. RESULTADOS: As medidas de peso corporal, indice de adiposidade, leptina e insulina aumentaram nos ratos OB, enquanto a pressao arterial permaneceu inalterada. A obesidade tambem produziu tolerância a glicose e resistencia a insulina. A reatividade a noradrenalina da aorta intacta foi similar em ratos C e OB. A presenca de L-NAME produziu um aumento similar nas respostas maximas, mas um desvio maior a esquerda das respostas nas aortas intactas dos ratos C em relacao aos ratos OB [EC50 (x10-7M): C = 1,84 (0,83-4,07), O = 2,49 (1,41-4,38); presenca de L-NAME C = 0,02 (0,01-0,04)*, O = 0,21 (0,11-0,40)*†,*p < 0,05 vs controle respectivo,†p < 0,05 vs controle mais L-NAME, n = 6-7]. Nenhum dos protocolos alterou a reatividade a noradrenalina de aortas com desnudamento. CONCLUSAO: A obesidade induzida por dieta rica em gordura promove alteracoes metabolicas e vasculares. A alteracao vascular envolveu uma melhora da via endotelial L-arginina/NO provavelmente relacionada a hiperinsulinemia e hiperleptinemia induzidas por dieta. A maior resistencia aos efeitos do L-NAME na aorta de ratos obesos diz respeito a menor vulnerabilidade de individuos obesos na presenca de patologias associadas que causam danos a atividade do sistema NO.BACKGROUND Mechanisms underlying vascular abnormalities in obesity remain to be completely clarified. OBJECTIVE L-arginine/nitric oxide pathway was evaluated on vascular response of high-fat diet-obese rats, focusing on endothelial and smooth muscle cells. METHODS 30-day-old rats were divided in two groups: control (C) and obese (OB, high-fat diet for 30 weeks). After 30 weeks, body weight, adiposity index, blood pressure, and metabolic and endocrine profiles of the animals were recorded. Curves to noradrenaline were obtained in absence and presence of nitric oxide synthase inhibitor (L-NAME, 3x10-4M) on intact and denuded thoracic aorta from C and OB rats. RESULTS Body weight, adiposity index, leptin and insulin levels were increased in OB, while blood pressure was unchanged. Obesity also produced glucose tolerance and insulin resistance. Reactivity to noradrenaline of intact aorta was similar in C and OB rats. L-NAME presence produced a similar increase in maximal responses, but a higher leftward shift of noradrenaline responses in intact aorta from C than in OB rats [EC50 (x10-7M): C = 1.84 (0.83-4.07), O = 2.49 (1.41-4.38); L-NAME presence C = 0.02 (0.01-0.04)*, O = 0.21 (0.11-0.40)**p < 0.05 vs respective control, p < 0.05 vs control plus L-NAME, n = 6-7]. None of the protocols altered the reactivity to noradrenaline of denuded aortas. CONCLUSION High-fat diet-induced obesity promotes metabolic and vascular alterations. The vascular alteration involved an endothelial L-arginine/NO pathway improvement was probably correlated to diet-induced hyperinsulinemia and hyperleptinemia. The greater resistance to L-NAME effects in aorta of obese rats raises concerns about the lower cardiovascular vulnerability of obese individuals in the presence of associated pathologies that impair NO-system activity.

Upregulation of mRNA myocardium calcium handling in rats submitted to exercise and food restriction

FUNDAMENTO: Treinamento fisico (TF) aumenta a sensibilidade dos hormonios tireoidianos (HT) e a expressao genica de estruturas moleculares envolvidas no movimento intracelular de calcio do miocardio, enquanto a restricao alimentar (RIA) promove efeitos contrarios ao TF. OBJETIVO: Avaliar os efeitos da associacao TF e RIA sobre os niveis plasmaticos dos HT e a producao de mRNA dos receptores HT e estruturas moleculares do movimento de calcio do miocardio de ratos. METODOS: Utilizaram-se ratos Wistar Kyoto divididos em: controle (C, n = 7), RIA (R50, n = 7), exercicio fisico (EX, n = 7) e exercicio fisico + RIA (EX50, n = 7). A RIA foi de 50% e o TF foi natacao (1 hora/dia, cinco sessoes/semana, 12 semanas consecutivas). Avaliaram-se as concentracoes sericas de triiodotironina (T3), tiroxina (T4) e hormonio tireotrofico (TSH). O mRNA da bomba de calcio do reticulo sarcoplasmatico (SERCA2a), fosfolamban (PLB), trocador Na+/Ca+2 (NCX), canal lento de calcio (canal-L), rianodina (RYR), calsequestrina (CQS) e receptor de HT (TRα1 e TRβ1) do miocardio foram avaliados por reacao em cadeia da polimerase (PCR) em tempo real. RESULTADOS: RIA reduziu o T4, TSH e mRNA do TRα1 e aumentou a expressao da PLB, NCX e canal-L. TF aumentou a expressao do TRβ1, canal-L e NCX. A associacao TF e RIA reduziu T4 e TSH e aumentou o mRNA do TRβ1, SERCA2a, NCX, PLB e correlacao do TRβ1 com a CQS e NCX. CONCLUSAO: Associacao TF e RIA aumentou o mRNA das estruturas moleculares calcio transiente, porem o eixo HT-receptor nao parece participar da transcricao genica dessas estruturas.BACKGROUND Chronic exercise and food restriction (FR) have directionally opposite changes in transcription of molecular structures of calcium handling and thyroid hormone (TH) status. OBJECTIVE Evaluate the association of chronic exercise and FR on serum thyroid hormones and gene transcription of molecular structures of intracellular calcium transients and thyroid receptors in myocardium of rats. METHODS Male Wistar Kyoto rats, divided into two groups: control (C, n = 7), FR (R50, n = 7), chronic exercise (EX, n = 7) and chronic exercise + FR (EX50, n = 7). FR was of 50% and exercise was swimming (1 hour/day, 5 days/week, during 12 weeks). Serum concentrations of T3, T4 and TSH were determined. The mRNA gene expression of the sarcoplasmatic reticulum calcium pump (SERCA2a), phospholamban (PLB), Na+/Ca+2 exchanger (NCX), calcium channel L-type (L-channel), ryanodine (RYR), calsequestrin (CQS) and HT receptor (TRα1 and TRβ1) of the myocardium was performed by PCR real-time. RESULTS FR reduced serum levels of T4 and TSH and TRα1 mRNA and increased the expression of PLB, NCX and L-channel. Exercise increased the TRβ1 receptor, L-channel and NCX. The association of exercise and FR reduced plasma T4 and TSH, TRβ1 mRNA increase, SERCA2a, NCX and PLB, and there was a significant correlation of TRβ1 with CQS and NXC. CONCLUSION Chronic exercise and food restriction increased the mRNA of transient Ca2+ proteins; however, TH-receptor axis cannot participate in the transcription of mRNA of myocardial calcium transient proteins.

Exercício e restrição alimentar aumentam o RNAm de proteínas do trânsito de Ca2+ miocárdico em ratos

FUNDAMENTO: Treinamento fisico (TF) aumenta a sensibilidade dos hormonios tireoidianos (HT) e a expressao genica de estruturas moleculares envolvidas no movimento intracelular de calcio do miocardio, enquanto a restricao alimentar (RIA) promove efeitos contrarios ao TF. OBJETIVO: Avaliar os efeitos da associacao TF e RIA sobre os niveis plasmaticos dos HT e a producao de mRNA dos receptores HT e estruturas moleculares do movimento de calcio do miocardio de ratos. METODOS: Utilizaram-se ratos Wistar Kyoto divididos em: controle (C, n = 7), RIA (R50, n = 7), exercicio fisico (EX, n = 7) e exercicio fisico + RIA (EX50, n = 7). A RIA foi de 50% e o TF foi natacao (1 hora/dia, cinco sessoes/semana, 12 semanas consecutivas). Avaliaram-se as concentracoes sericas de triiodotironina (T3), tiroxina (T4) e hormonio tireotrofico (TSH). O mRNA da bomba de calcio do reticulo sarcoplasmatico (SERCA2a), fosfolamban (PLB), trocador Na+/Ca+2 (NCX), canal lento de calcio (canal-L), rianodina (RYR), calsequestrina (CQS) e receptor de HT (TRα1 e TRβ1) do miocardio foram avaliados por reacao em cadeia da polimerase (PCR) em tempo real. RESULTADOS: RIA reduziu o T4, TSH e mRNA do TRα1 e aumentou a expressao da PLB, NCX e canal-L. TF aumentou a expressao do TRβ1, canal-L e NCX. A associacao TF e RIA reduziu T4 e TSH e aumentou o mRNA do TRβ1, SERCA2a, NCX, PLB e correlacao do TRβ1 com a CQS e NCX. CONCLUSAO: Associacao TF e RIA aumentou o mRNA das estruturas moleculares calcio transiente, porem o eixo HT-receptor nao parece participar da transcricao genica dessas estruturas.BACKGROUND Chronic exercise and food restriction (FR) have directionally opposite changes in transcription of molecular structures of calcium handling and thyroid hormone (TH) status. OBJECTIVE Evaluate the association of chronic exercise and FR on serum thyroid hormones and gene transcription of molecular structures of intracellular calcium transients and thyroid receptors in myocardium of rats. METHODS Male Wistar Kyoto rats, divided into two groups: control (C, n = 7), FR (R50, n = 7), chronic exercise (EX, n = 7) and chronic exercise + FR (EX50, n = 7). FR was of 50% and exercise was swimming (1 hour/day, 5 days/week, during 12 weeks). Serum concentrations of T3, T4 and TSH were determined. The mRNA gene expression of the sarcoplasmatic reticulum calcium pump (SERCA2a), phospholamban (PLB), Na+/Ca+2 exchanger (NCX), calcium channel L-type (L-channel), ryanodine (RYR), calsequestrin (CQS) and HT receptor (TRα1 and TRβ1) of the myocardium was performed by PCR real-time. RESULTS FR reduced serum levels of T4 and TSH and TRα1 mRNA and increased the expression of PLB, NCX and L-channel. Exercise increased the TRβ1 receptor, L-channel and NCX. The association of exercise and FR reduced plasma T4 and TSH, TRβ1 mRNA increase, SERCA2a, NCX and PLB, and there was a significant correlation of TRβ1 with CQS and NXC. CONCLUSION Chronic exercise and food restriction increased the mRNA of transient Ca2+ proteins; however, TH-receptor axis cannot participate in the transcription of mRNA of myocardial calcium transient proteins.

Digoxin Induces Cardiac Hypertrophy Without Negative Effects on Cardiac Function and Physical Performance in Trained Normotensive Rats.

Cardiotonic drugs and exercise training promote cardiac inotropic effects, which may affect training-induced cardiac adaptations. This study investigated the effects of long-term administration of digoxin on heart structure and function, and physical performance of rats submitted to high-intensity interval training (HIIT). Male Wistar rats, 60 days old, were divided into control (C), digoxin (DIGO), trained (T), and trained with digoxin (TDIGO). Digoxin was administered by gavage (30 µg/kg/day) for 75 days. The HIIT program consisted of treadmill running 60 min/day (8 min at 80% of the maximum speed (MS) and 2 min at 20% of the MS), 5 days per week during 60 days. The main cardiac parameters were evaluated by echocardiograph and cardiomyocyte area was determined by histology. There were no group x time effects of digoxin, HIIT or interactions (digoxin and HIIT) on functional echocardiographic parameters (heart rate; ejection fraction) or in the maximum exercise test. There was a group x time interaction, as evidenced by observed cardiac hypertrophy in the TDIGO group evaluated by ratio of left ventricle weight to body weight (p<0.002) and cardiomyocyte area (p<0.000002). Long-term administration of digoxin promoted cardiac hypertrophy without affecting cardiac function and physical performance in rats submitted to HIIT.

Fasting/Refeeding Cycles Prevent Myocardial Dysfunction and Morphology Damage in the Spontaneously Hypertensive Rats

Background Caloric restriction is known to impair the cardiac function and morphology in hypertrophied hearts of spontaneously hypertensive rats (SHR); however, the influence of fasting/refeeding (RF) is unknown. Objective To investigate the fasting/refeeding approach on myocardial remodeling and function. In addition, the current study was designed to bring information regarding the mechanisms underlying the participation of Ca2+ handling and β-adrenergic system. Methods Sixty-day-old male SHR rats were submitted to food ad libitum (C), 50% food restriction (R50) or RF cycles for 90 days. Cardiac remodeling was assessed by ultrastructure analysis and isolated papillary muscle function. The level of significance considered was 5% (α = 0.05). Results The RF rats presented lower cardiac atrophy than R50 in relation to C rats. The C rats increased weight gain, R50 maintained their initial body weight and RF rats increased and decreased weight during RF. The RF did not cause functional impairment because the isotonic and isometric parameters showed similar behavior to those of C. The isotonic and isometric cardiac parameters were significantly elevated in RF rats compared to R50 rats. In addition, the R50 rats had cardiac damage in relation to C for isotonic and isometric variables. While the R50 rats showed focal changes in many muscle fibers, the RF rats displayed mild alterations, such as loss or disorganization of myofibrils. Conclusion Fasting/refeeding promotes cardiac beneficial effects and attenuates myocardial injury caused by caloric restriction in SHR rats, contributing to reduce the cardiovascular risk profile and morphological injuries. Furthermore, RF promotes mild improvement in Ca2+ handling and β-adrenergic system.

O Programa de Pós-Graduação em Educação Física / UFES: Pesquisa e ensino em atividade física & saúde

A pesquisa e a formacao de recursos humanos em atividade fisica e saude tem importância significativa para o desenvolvimento da pos-graduacao em educacao fisica no pais. O presente artigo apresenta os laboratorios e linhas de pesquisa do Programa de Pos-Graduacao em Educacao Fisica da Universidade Federal do Espirito Santo (PPGEF/UFES) com aderencia a esta tematica. Sao descritos o contexto, acoes e motivacoes que possibilitaram a abertura da area de concentracao em Educacao Fisica, movimento corporal humano e saude , suas respectivas linhas de pesquisa, os principios gerais adotados na formacao de novos pesquisadores, as tematicas especificas de cada grupo e as parcerias e redes de pesquisa estabelecidas. Como conclusao, indicamos o potencial de contribuicao das linhas de pesquisa do PPGEF/UFES para o conhecimento sobre o tema e o desenvolvimento regional.

Ejercicio y restricción alimenticia aumentan el rnam de proteínas del tránsito de Ca2+ miocárdico en ratones

FUNDAMENTO: Treinamento fisico (TF) aumenta a sensibilidade dos hormonios tireoidianos (HT) e a expressao genica de estruturas moleculares envolvidas no movimento intracelular de calcio do miocardio, enquanto a restricao alimentar (RIA) promove efeitos contrarios ao TF. OBJETIVO: Avaliar os efeitos da associacao TF e RIA sobre os niveis plasmaticos dos HT e a producao de mRNA dos receptores HT e estruturas moleculares do movimento de calcio do miocardio de ratos. METODOS: Utilizaram-se ratos Wistar Kyoto divididos em: controle (C, n = 7), RIA (R50, n = 7), exercicio fisico (EX, n = 7) e exercicio fisico + RIA (EX50, n = 7). A RIA foi de 50% e o TF foi natacao (1 hora/dia, cinco sessoes/semana, 12 semanas consecutivas). Avaliaram-se as concentracoes sericas de triiodotironina (T3), tiroxina (T4) e hormonio tireotrofico (TSH). O mRNA da bomba de calcio do reticulo sarcoplasmatico (SERCA2a), fosfolamban (PLB), trocador Na+/Ca+2 (NCX), canal lento de calcio (canal-L), rianodina (RYR), calsequestrina (CQS) e receptor de HT (TRα1 e TRβ1) do miocardio foram avaliados por reacao em cadeia da polimerase (PCR) em tempo real. RESULTADOS: RIA reduziu o T4, TSH e mRNA do TRα1 e aumentou a expressao da PLB, NCX e canal-L. TF aumentou a expressao do TRβ1, canal-L e NCX. A associacao TF e RIA reduziu T4 e TSH e aumentou o mRNA do TRβ1, SERCA2a, NCX, PLB e correlacao do TRβ1 com a CQS e NCX. CONCLUSAO: Associacao TF e RIA aumentou o mRNA das estruturas moleculares calcio transiente, porem o eixo HT-receptor nao parece participar da transcricao genica dessas estruturas.BACKGROUND Chronic exercise and food restriction (FR) have directionally opposite changes in transcription of molecular structures of calcium handling and thyroid hormone (TH) status. OBJECTIVE Evaluate the association of chronic exercise and FR on serum thyroid hormones and gene transcription of molecular structures of intracellular calcium transients and thyroid receptors in myocardium of rats. METHODS Male Wistar Kyoto rats, divided into two groups: control (C, n = 7), FR (R50, n = 7), chronic exercise (EX, n = 7) and chronic exercise + FR (EX50, n = 7). FR was of 50% and exercise was swimming (1 hour/day, 5 days/week, during 12 weeks). Serum concentrations of T3, T4 and TSH were determined. The mRNA gene expression of the sarcoplasmatic reticulum calcium pump (SERCA2a), phospholamban (PLB), Na+/Ca+2 exchanger (NCX), calcium channel L-type (L-channel), ryanodine (RYR), calsequestrin (CQS) and HT receptor (TRα1 and TRβ1) of the myocardium was performed by PCR real-time. RESULTS FR reduced serum levels of T4 and TSH and TRα1 mRNA and increased the expression of PLB, NCX and L-channel. Exercise increased the TRβ1 receptor, L-channel and NCX. The association of exercise and FR reduced plasma T4 and TSH, TRβ1 mRNA increase, SERCA2a, NCX and PLB, and there was a significant correlation of TRβ1 with CQS and NXC. CONCLUSION Chronic exercise and food restriction increased the mRNA of transient Ca2+ proteins; however, TH-receptor axis cannot participate in the transcription of mRNA of myocardial calcium transient proteins.

Alteraciones vasculares en ratones obesos por dieta rica en grasa: papel de la vía L-arginina/NO endotelial

FUNDAMENTO: Mecanismos subjacentes a anormalidades vasculares na obesidade ainda nao estao completamente esclarecidos. OBJETIVO: Foi avaliada a via do oxido nitrico/L-arginina na resposta vascular de ratos obesos por dieta rica em gordura, enfocando as celulas endoteliais e do musculo liso. METODOS: Ratos com 30 dias de vida foram divididos em 2 grupos: controle (C) e obeso (OB, ratos sob dieta rica em gordura por 30 semanas). Apos 30 semanas, foram registrados o peso corporal, indice de adiposidade, pressao arterial e perfis metabolicos e endocrinos dos animais. Foram obtidas curvas para noradrelanina na ausencia e presenca de inibidor de oxido nitrico sintase (L-NAME, 3x10-4M) em aorta toracica intacta e com desnudamento em ratos C e OB. RESULTADOS: As medidas de peso corporal, indice de adiposidade, leptina e insulina aumentaram nos ratos OB, enquanto a pressao arterial permaneceu inalterada. A obesidade tambem produziu tolerância a glicose e resistencia a insulina. A reatividade a noradrenalina da aorta intacta foi similar em ratos C e OB. A presenca de L-NAME produziu um aumento similar nas respostas maximas, mas um desvio maior a esquerda das respostas nas aortas intactas dos ratos C em relacao aos ratos OB [EC50 (x10-7M): C = 1,84 (0,83-4,07), O = 2,49 (1,41-4,38); presenca de L-NAME C = 0,02 (0,01-0,04)*, O = 0,21 (0,11-0,40)*†,*p < 0,05 vs controle respectivo,†p < 0,05 vs controle mais L-NAME, n = 6-7]. Nenhum dos protocolos alterou a reatividade a noradrenalina de aortas com desnudamento. CONCLUSAO: A obesidade induzida por dieta rica em gordura promove alteracoes metabolicas e vasculares. A alteracao vascular envolveu uma melhora da via endotelial L-arginina/NO provavelmente relacionada a hiperinsulinemia e hiperleptinemia induzidas por dieta. A maior resistencia aos efeitos do L-NAME na aorta de ratos obesos diz respeito a menor vulnerabilidade de individuos obesos na presenca de patologias associadas que causam danos a atividade do sistema NO.BACKGROUND Mechanisms underlying vascular abnormalities in obesity remain to be completely clarified. OBJECTIVE L-arginine/nitric oxide pathway was evaluated on vascular response of high-fat diet-obese rats, focusing on endothelial and smooth muscle cells. METHODS 30-day-old rats were divided in two groups: control (C) and obese (OB, high-fat diet for 30 weeks). After 30 weeks, body weight, adiposity index, blood pressure, and metabolic and endocrine profiles of the animals were recorded. Curves to noradrenaline were obtained in absence and presence of nitric oxide synthase inhibitor (L-NAME, 3x10-4M) on intact and denuded thoracic aorta from C and OB rats. RESULTS Body weight, adiposity index, leptin and insulin levels were increased in OB, while blood pressure was unchanged. Obesity also produced glucose tolerance and insulin resistance. Reactivity to noradrenaline of intact aorta was similar in C and OB rats. L-NAME presence produced a similar increase in maximal responses, but a higher leftward shift of noradrenaline responses in intact aorta from C than in OB rats [EC50 (x10-7M): C = 1.84 (0.83-4.07), O = 2.49 (1.41-4.38); L-NAME presence C = 0.02 (0.01-0.04)*, O = 0.21 (0.11-0.40)**p < 0.05 vs respective control, p < 0.05 vs control plus L-NAME, n = 6-7]. None of the protocols altered the reactivity to noradrenaline of denuded aortas. CONCLUSION High-fat diet-induced obesity promotes metabolic and vascular alterations. The vascular alteration involved an endothelial L-arginine/NO pathway improvement was probably correlated to diet-induced hyperinsulinemia and hyperleptinemia. The greater resistance to L-NAME effects in aorta of obese rats raises concerns about the lower cardiovascular vulnerability of obese individuals in the presence of associated pathologies that impair NO-system activity.