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Estrogen protects transgenic hypertensive rats by shifting the vasoconstrictor-vasodilator balance of RAS

Item Type:Article
Title:Estrogen protects transgenic hypertensive rats by shifting the vasoconstrictor-vasodilator balance of RAS
Creators Name:Brosnihan, K.B. and Li, P. and Ganten, D. and Ferrario, C.M.
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 17 beta-estradiol (1.5 mg/rat s.c. 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.
Keywords:Angiotensin II, Genetically Modified Animals, Thoracic Aorta, Blood Pressure, Estradiol, Estrogen Replacement Therapy, Hypertension, Kidney, Cardiovascular Models, Smooth, Vascular Muscle, Ovariectomy, Peptide Fragments, Peptidyl-Dipeptidase A, Renin, Renin-Angiotensin System, Vasoconstriction, Vasodilation, Animals, Mice, Rats
Source:American Journal of Physiology Regulatory Integrative and Comparative Physiology
ISSN:0363-6119
Publisher:American Physiological Society (U.S.A.)
Volume:273
Number:6 Pt 2
Page Range:R1908-R1915
Date:1 December 1997
Official Publication:http://ajpregu.physiology.org/cgi/content/abstract/273/6/R1908
PubMed:View item in PubMed

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