Vasodilator Effect of Angiotensin-(1-7) on Vascular Coronary Bed of Rats: Role of Mas, ACE and ACE2.

BACKGROUND: Angiotensin(Ang)-(1-7) is a biologically active member of the reninangiotensin system that participates of the regulation of blood pressure. Although Ang-(1-7) is able to potentiate the vasodilator effect of bradykinin in coronary bed of rats, a direct vasodilator effect of Ang-(1-7) in this vascular bed has not been characterized. OBJECTIVES: The aim of this study was to evaluate the mechanisms involved in the vasodilator effect of Ang-(1-7) in the vasculature of isolated rat hearts perfused according to the Langendorff technique at constant flow. METHODS: Isolated hearts, after approximately 30 minutes of stabilization, were perfused with Krebs-Ringer solution (KRS) alone (control) or KRS containing Ang-(1-7). The participation of the Ang-(1-7) receptor Mas, AT1 receptor, angiotensin-converting enzyme (ACE) and ACE2 was evaluated perfusing hearts with a combination of Ang-(1-7) plus A779, Ang-(1-7) plus losartan, Ang-(1-7) plus captopril/enalapril and Ang-(1-7) plus DX-600, respectively. RESULTS: Ang-(1-7) induced a significant decrease in the perfusion pressure, indicating a direct vasodilatation action of this peptide in the coronary bed. This effect was abolished by A779, captopril, enalapril and DX-600 an ACE2-specific inhibitor. However, AT1 blockade did not blunt the Ang-(1-7) effect. No significant changes were observed in heart rate, as well as in contractile tension and ±dT/dt. Moreover, immunohistochemical analysis showed the presence of Ang-(1-7) and Mas in coronary vessels. CONCLUSION: The Ang-(1-7) concentration used in this study was unable to induce changes in the cardiac function since no consistent alterations in contraction force and HR were viewed after Ang- (1-7) perfusion. In summary, this study showed that Ang-(1-7) induces vasodilation in the coronary bed of rats and this effect involves coupling to Mas receptor and interaction with ACE and ACE2.

Effects of severe caloric restriction from birth on the hearts of adult rats.

There has been increasing evidence suggesting that a severe caloric restriction (SCR) (above 40%) has beneficial effects on the hearts of rats. However, most of the reports have focused on the effects of SCR that started in adulthood. We investigated the consequences of SCR on the hearts of rats subjected to SCR since birth (CR50). From birth to the age of 3 months, CR50 rats were fed 50% of the food that the ad libitum group (AL) was fed. Thereafter, a maximal aerobic test was performed to indirectly evaluate global cardiovascular function. Indices of contractility (+dT/dt) and relaxation (-dT/dt) were analyzed in isolated heart preparation, and cardiomyocyte diameter, number, density, and myocardium collagen content were obtained through histologic analysis. Ventricular myocytes were isolated, using standard methods to evaluate phosphorylated AKT levels, and Ca(2+) handling was evaluated with a combination of Western blot analysis, intracellular Ca(2+) imaging, and confocal microscopy. CR50 rats exhibited increased aerobic performance and cardiac function, as shown by the increase in ±dT/dt. Despite the smaller cardiomyocyte diameter, CR50 rats had an increased heart-body weight ratio, increased cardiomyocyte density and number, and similar levels of myocardium collagen content, compared with AL rats. AKT was hyperphosphorylated in cardiomyocytes from CR50 rats, and there were no significant differences in Ca(2+) transient and SERCA2 levels in cardiomyocytes between CR50 and AL rats. Collectively, these observations reveal the beneficial effects of a 50% caloric restriction on the hearts of adult rats restricted since birth, which might involve cardiomyocyte AKT signaling.