Estrogen replacement in ovariectomized monkeys and hypertensive rats reduced ACE activity and Ang II levels while increasing vasodilator Ang-(1-7), promoting an anti-hypertensive effect.
Estrogen stimulates the renin-angiotensin system by augmenting both tissue and circulating levels of angiotensinogen and renin. We show, however, that angiotensin converting enzyme (ACE) activity in the circulation and in tissues is reduced in two animal models of postmenopausal chronic hormone replacement. We observed a reduction of ACE activity in association with a significant increase in plasma angiotensin I (Ang I) and hyperreninemia in ovariectomized monkeys treated with Premarin (conjugated equine estrogen) replacement for 30 months. Plasma angiotensin II (Ang II) levels were not increased in monkeys treated with estrogen, suggesting that the decrease in ACE curtailed the formation of the peptide. The Ang II/Ang I ratio, an in vivo index of ACE activity, was significantly reduced by estrogen treatment, further supporting the biochemical significance of estrogen's inhibition of ACE. In ovariectomized transgenic hypertensive (mRen2)27 rats submitted to estrogen replacement treatment for 3 weeks, ACE activity in plasma and tissue (aorta and kidney) and circulating Ang II levels were reduced, whereas circulating levels of angiotensin-(1-7) (Ang-(1-7)) were increased. Ang-(1-7), the N-terminal fragment of Ang II, is a novel vasodilator and antihypertensive peptide. Thus, the net balance of these effects of estrogen on the reninangiotensin vasoconstrictor/vasodilator system is to promote the anti-hypertensive effect.
Brosnihan et al. (Thu,) conducted a other in Postmenopausal chronic hormone replacement models. Estrogen replacement (Premarin / conjugated equine estrogen) was evaluated on ACE activity in the circulation and in tissues. Estrogen replacement in ovariectomized monkeys and hypertensive rats reduced ACE activity and Ang II levels while increasing vasodilator Ang-(1-7), promoting an anti-hypertensive effect.