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 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
K B
KB
Hypertension and Vascular Disease Center, Wake Forest University School of Medicine, Winston-Salem, NC, USA. bbrosnih@wfubmc.edu
Senanayake
P S
PS
Li
P
P
Ferrario
C M
CM
D000809:Angiotensins / Q000032:analysis; D000818:Animals; D001013:Aorta, Thoracic / Q000201:enzymology; D015914:Estrogen Replacement Therapy; D004967:Estrogens / Q000502:physiology*; D005260:Female; D000882:Haplorhini; D007668:Kidney / Q000201:enzymology; D010052:Ovariectomy; D007703:Peptidyl-Dipeptidase A; D010949:Plasma / Q000201:enzymology; D051381:Rats; D012084:Renin-Angiotensin System / Q000502:physiology*; D014662:Vasoconstrictor Agents / Q000032:analysis
D000809:Angiotensins; D004967:Estrogens; D014662:Vasoconstrictor Agents; D007703:Peptidyl-Dipeptidase A