Affiliation:
1. The Hypertension Center, Bowman Gray School of Medicine, Wake Forest University, Winston-Salem, North Carolina 27157-1032
Abstract
In pursuit of the hypothesis that estrogen shifts the vasoconstrictor-vasodilator balance of the renin-angiotensin system, we investigated the cardiovascular responses to administration of angiotensin-(1—7) [ANG-(1—7)] and angiotensin II (ANG II) in female transgenic (mRen2)27-positive [Tg(+)] and -negative [Tg(−)] rats in the presence and absence of 3 wk of estrogen replacement therapy. Fifty-three female Tg(−) and Tg(+) rats were oophorectomized and received either 17β-estradiol (1.5 mg/rat sc for 3 wk) or vehicle. At the end of 3 wk of estrogen treatment, mean blood pressure was lowered in freely moving chronically cannulated Tg(+) (159 ± 4 vs. 145 ± 5 mmHg, P < 0.05) and Tg(−) (119 ± 4 vs. 108 ± 2 mmHg, P < 0.05) rats. Moreover, the magnitude of the depressor component of the biphasic response to ANG-(1—7) was significantly enhanced in estrogen-treated Tg(+) rats, whereas the pressor component to ANG-(1—7) was attenuated in both Tg(+) and Tg(−) rats. Estrogen replacement significantly attenuated the pressor response to ANG II in both Tg(+) and Tg(−) rats. In addition, estrogen replacement therapy significantly reduced plasma ANG-converting enzyme activity in association with a reduction in circulating levels of ANG II. Tissue levels (kidney and aorta) of ANG-converting enzyme were also reduced with chronic estrogen replacement therapy. On the other hand, estrogen augmented the levels of plasma ANG-(1—7) in Tg(+) animals. Plasma renin activity was unchanged with estrogen treatment. These findings provide the first evidence demonstrating that estrogen is protective against hypertension, possibly by amplifying the vasodilator contributions of ANG-(1—7), while reducing the formation and vasoconstrictor actions of ANG II.
Publisher
American Physiological Society
Subject
Physiology (medical),Physiology
Cited by
123 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献