ESTROGEN PROTECTS TRANSGENIC HYPERTENSIVE RATS BY SHIFTING THE VASOCONSTRICTOR-VASODILATOR BALANCE OF RAS

In pursuit of the hypothesis that estrogen shifts the vasoconstrictor- vasodilator balance of the renin-angiotensin system, we investigated t he cardiovascular responses to administration of angiotensin(1-7) [ANG -(1-7)] and angiotensin II (ANG II) in female transgenic (mRen2)27-pos itive [Tg(+)] and -negative [Tg(-)] rats in the presence and absence o f 3 wk of estrogen replacement therapy. Fifty-three female Tg(-) and T g(+) rats were oophorectomized and received either 17 beta-estradiol ( 1.5 mg/rat sc for 3 wk) or vehicle. At the end of 3 wk of estrogen tre atment, mean blood pressure was lowered in freely moving chronically c annulated Tg(+) (159 +/- 4 vs. 145 +/- 5 mmHg, P < 0.05) and Tg(-) (11 9 +/- 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 sig nificantly enhanced in estrogen-treated Tg(+) rats, whereas the presse r component to ANG-(1-7) was attenuated in both Tg(+) and Tg(-) rats. Estrogen replacement significantly attenuated the presser response to ANG II in both Tg(+) and Tg(-) rats. In addition, estrogen replacement therapy significantly reduced plasma ANG-converting enzyme activity i n 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 ren in activity was unchanged with estrogen treatment. These findings prov ide the first evidence demonstrating that estrogen is protective again st hypertension, possibly by amplifying the vasodilator contributions of ANG-(1-7), while reducing the formation and vasoconstrictor actions of ANG II.