Bi-directional actions of estrogen on the renin-angiotensin system

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 tis sues is reduced in two animal models of postmenopausal chronic hormone repl acement. We observed a reduction of ACE activity in association with a sign ificant increase in plasma angiotensin I (Ang I) and hyperreninemia in ovar iectomized monkeys treated with Premarin (conjugated equine estrogen) repla cement for 30 months. Plasma angiotensin II (Ang IT) levels were not increa sed in monkeys treated with estrogen, suggesting that the decrease in ACE c urtailed the formation of the peptide. The Ang II/ng I ratio, an in vivo in dex of ACE activity, was significantly reduced by estrogen treatment, furth er supporting the biochemical significance of estrogen's inhibition of ACE. In ovariectomized transgenic hypertensive (mRen2)27 rats submitted to estr ogen replacement treatment for 3 weeks, ACE activity in plasma and tissue ( aorta and kidney) and circulating Ang II levels were reduced, whereas circu lating levers of angiotensin-(1-7) (Ang-(1-7)) were increased. Ang-(1-7), t he N-terminal fragment of Ang TI, is a novel vasodilator and antihypertensi ve peptide. Thus, the net balance of these effects of estrogen on the renin -angiotensin vasoconstrictor/vasodilator system is to promote the antihyper tensive effect.