Hypotensive effect of angiotensin-(1-7) in sinoartic denervated rats

GIRONACCI MM, HOCHT C, MAYER M, TAIRA CA.

Miami, USA

Congreso; XVIIth Scientific Sessions of the Inter-American Society of Hypertension; 2007

Inter-American Society of Hypertension

HYPOTENSIVE EFFECT OF ANGIOTENSIN-(1-7) IN SINOARTIC DENERVATED RATS MARIELA M. GIRONACCI, Christian Höcht, Marcos A. Mayer, Carlos Taira Dpto. Qca. Biológica y Farmacología, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires, Argentina. Background: The sinoartic denervated rat (SAD) is an experimental model of hypertension characterized by an increase in blood pressure variability rather than a sustained hypertensive stage. Among the different mechanisms involved in the high blood pressure variability-induced end-organ damage, activation of the renin-angiotensin system (RAS) plays an important role. In fact, SAD rats exhibit enhanced sensitivity to the central pressor effects of angiotensin (Ang) II. Objective: Our aim was to investigate the role of Ang-(1-7), an antihypertensive component of the RAS which was suggested to counteract Ang II pressor actions, in the hypothalamus of SAD rats. Furthermore, since it has been demonstrated that Ang converting enzyme (ACE) inhibitors increase endogenous levels of Ang-(1-7), we addressed the involvement of Ang-(1-7) in the hypotensive effect induced by captopril in SAD rats. Methods: Wistar rats 7 days after sinoartic denervation or sham operation were employed. They were anaesthetized with chloralose-urethane and the carotid artery was cannulated for monitoring mean arterial pressure (MAP). A stainless-steel needle was inserted into the anterior hypothalamic for drug administration. Results: MAP basal values and heart rate were not different between animals subjected to sham operation and those with sinoartic denervation (87±4 mmHg and 413±12 bpm in anaesthetized SO versus 91±2 mmHg and 425±15 bpm in anaesthetized SAD rats). The intrahypothalamic administration of 5 pmol Ang‑(1‑7) was without effect in SO rats but reduced MAP in SAD rats by 15.5 ± 3.2  mmHg (p<0.05). The reduction in blood pressure caused by Ang-(1-7) in SAD rats was blocked by 250 pmol [D-Ala7]-Ang-(1-7), a specific antagonist of Ang-(1-7) receptors, the Mas receptors. Ang II (50 pmol) induced an increase in blood pressure in both groups being its pressor response greater in SAD rats (DMAP = 9.6 ± 1.0 in SO rats vs 15.8 ± 1.4 in SAD rats). The pressor response elicited by Ang II  in SO rats was not modified when it was coadminestered with Ang-(1-7). However, the heptapeptide partially abolished the increase in blood pressure caused by Ang II in SAD rats. While the intrahypothalamic injection of 50 nmol captopril did not affect blood pressure in SO animals, it significantly reduced MAP in SAD rats (DMAP = -13.3 ± 1.9 p<0.05). The antagonist of Ang-(1-7) receptor partially blocked the reduction in MAP caused by captopril. Conclusions: Our results demonstrate that intrahypothalamic application of Ang-(1-7) exerted a hypotensive effect and blocked the Ang II pressor response in SAD rats via Mas receptors activation contributing in this way to blood pressure regulation. The hepateptide is also involved in the hypotensive effect of the ACE inhibitor in rats with SAD.