RESUMO
Exercise training leads to physiological cardiac hypertrophy and the protective axis of the renin-angiotensin system composed of angiotensin-converting enzyme 2, angiotensin-(1-7), and Mas receptor seems involved in this process. However, the role of the basal activity of the Mas receptor in exercise-induced physiological cardiac hypertrophy is still unclear. We evaluated the effects of the Mas receptor blockade on the left ventricular structure and function of rats submitted to running training. Rats were assigned to 4 groups: sedentary (S), sedentary + A-779 (Mas receptor antagonist, 120⯵g/kg/day, i.p.; SA), trained (60-minute treadmill running sessions, five days a week, 8 weeks; T), and trained + A-779 (TA). Systolic blood pressure was higher in sedentary and trained rats treated with A-779 at the end of the experimental period. The A-779 treatment prevented the left ventricular hypertrophy evoked by physical exercise and increased collagen deposition in sedentary and trained rats. Cardiomyocytes from the SA group presented increased length and thickness of the sarcomeres, elongated mitochondria, glycogen deposits, and enlarged cisterns of the sarcoplasmic reticulum. TA group presented a reduced sarcomere thickness and cytoplasm with a degenerative aspect. These findings show that the basal activity of the Mas receptor is essential for the proper turnover of the extracellular matrix in the myocardium and the maintenance of the sarcomeric structure of cardiomyocytes.
Assuntos
Cardiomegalia , Condicionamento Físico Animal , Proto-Oncogene Mas , Proteínas Proto-Oncogênicas , Ratos Wistar , Receptores Acoplados a Proteínas G , Animais , Ratos , Masculino , Receptores Acoplados a Proteínas G/metabolismo , Receptores Acoplados a Proteínas G/antagonistas & inibidores , Proteínas Proto-Oncogênicas/metabolismo , Cardiomegalia/metabolismo , Cardiomegalia/induzido quimicamente , Cardiomegalia/patologia , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/patologia , Pressão Sanguínea/efeitos dos fármacos , Hipertrofia Ventricular Esquerda/metabolismo , Hipertrofia Ventricular Esquerda/patologia , Fragmentos de Peptídeos/farmacologia , Fragmentos de Peptídeos/metabolismo , Angiotensina II/análogos & derivadosRESUMO
In this study, we tested the hypothesis that angiotensin-(1-7) [Ang-(1-7)] acting in the neurons of paraventricular hypothalamic nucleus (PVN) contributes to the maintenance of sympathetic activity and blood pressure. For this purpose, the effects of microinjection of the A-779, the receptor Mas antagonist, into the PVN on mean arterial pressure (MAP), heart rate (HR), and renal sympathetic nerve activity (RSNA) were evaluated. In rats anesthetized with urethane (1.2 to 1.4 g/kg IP), bilateral microinjections of A-779 (0.1 nmol) into the PVN resulted in a selective and significant decrease in RSNA (-26+/-6% versus -2+/-3% vehicle; saline 0.9%). The magnitude of the decrease in RSNA produced by A-779 was comparable to that observed after microinjection of muscimol (1 nmol; -26+/-4%), a powerful neuronal inhibitor. A higher dose of A-779 (1 nmol) caused a reduction in RSNA (-21+/-4%) that was comparable in magnitude to the reduction observed with the lower dose. When compared with vehicle solution, no significant changes in MAP or HR were observed with both doses of A-779 tested. A decrease in RSNA was also observed after microinjections into the PVN of the angiotensin II type 2 (AT2) receptor antagonist PD123319 (1 nmol; -18+/-4%). Microinjections of the AT1 antagonist losartan but not CV 11974 reduced MAP without changing RSNA. These results suggest that Ang-(1-7) Mas receptors and AT2 receptors in the PVN neurons play a role in mediating the tonic maintenance of RSNA.