Abstract 388: ICV Angiotensin-(1-7) Improves Cardiac Function and Attenuates Remodeling In (mren2)27 Transgenic Hypertensive Rats

Abstract

Overactivity of the renin-angiotensin system (RAS), through Ang II/AT1 axis, plays a critical role in the pathogenesis of cardiovascular diseases. On the other hand, Ang-(1-7)/Mas axis is recognized to attenuate the deleterious effects of the RAS at different sites including the central nervous system. In the present study, Sprague Dawley (SD) and transgenic hypertensive rats (mRen2)27, instrumented with telemetry probes for arterial pressure (AP) measurements, were subjected to 14 days of lateral ventricle (ICV) infusion of Ang-(1-7) (200 ng/h) alone, Ang-(1-7) (200 ng/h) in association with a Mas receptor antagonist (A779, 1 μg/h) or saline (0.5 ml/hour) through osmotic mini-pumps. Ang-(1-7) ICV attenuated hypertension of (mRen2)27 rats (144±8 mmHg vs 174±3 mmHg, before. The AP lowering effect of ICV Ang-(1-7) was completely blocked by A779 (174±12 mmHg). Cardiac hypertrophy and dysfunction, evaluated by echocardiography, of (mRen2)27 rats were attenuated in Ang-(1-7) infused rats. The increased levels of atrial natriuretic peptide, brain natriuretic peptide, collagen I, fibronectin and TGF-β1 in the heart of (mRen2)27 rats were significantly reduced by Ang-(1-7) infusion and partially reversed by the concomitant infusion of A-779. Further, cardiac effects induced by ICV Ang-(1-7) were accompanied by an attenuation of the increased ratio sympathetic/ vagal activity to the heart of (mRen2)27. The data of the present study indicate that short-term central infusion of Ang-(1-7) produces Mas-mediate improvement in cardiac function and attenuates cardiac remodeling in (mRen2)27 hypertensive rats, probably through an improvement of the autonomic balance to the heart. Support: CAPES and FAPEMIG/CNPq through INCT-NanoBioFar and PRONEX.