Abstract 441: Central Infusion of Angiotensin(1-7) Attenuates Aldosterone/Salt-Induced Increases in Blood Pressure in Ovariectomized Female Rats

Abstract

In comparison to male rodents, females are protected against angiotensin II (ANG II)- and aldosterone (Aldo)-induced hypertension. However, the mechanism underlying this protective effect is not well understood. ANG(1-7) is formed from ANG II by angiotensin converting enzyme 2 (ACE2) and plays an anti-hypertensive effect in the CNS. Recent studies from our laboratory demonstrate that central blockade ANG(1-7) augments Aldo-induced hypertension in intact female rats. The present study further determined whether central infusion of ANG(1-7) will attenuate Aldo/salt-induced increase in blood pressure (BP) in ovariectomized (OVX) female rats. Systemic infusion of Aldo (0.75 μg/h, 4 weeks) into OVX female rats with 1% salt as their sole drinking fluid resulted in a significant increase in BP (Δ26.9±2.9 mmHg). Central infusion of ANG(1-7) significantly attenuated this Aldo/salt pressor effect (Δ11.9±2.8 mmHg). RT-PCR analysis revealed that mRNA expression of renin (from 3.6 to1.1-fold) and ACE1 (from 2.6 to 0.9-fold) were significantly reduced in Aldo/salt treated rats with central infusion of ANG(1-7) when compared with central vehicle infusion. In contrast, mRNA expression of ACE2 (from 1.0 to 1.4-fold), AT 2 R (from 0.4 to 1.2-fold) and estrogen receptor alpha (ERα, from 0.9 to 1.7-fold) were significantly increased in the lamina terminalis. Taken together these results suggest that a central antihypertensive arm of the brain renin-angiotensin system (ACE2/ANG(1-7)/Mas) may play an important compensatory role in the development of Aldo/salt induced hypertension in females. (HL-14388, HL-98207, DK-66086, and MH-80241)