Physiological levels of estrogen appear to enhance angiotensin type 2 receptor- (AT2R-) mediated vasodilatation. However,\nthe effects of supraphysiological levels of estrogen, analogous to those achieved with high-dose estrogen replacement therapy\nin postmenopausal women, remain unknown. Therefore, we pretreated ovariectomized rats with a relatively high dose of\nestrogen (0.5mg/kg/week) for two weeks. Subsequently, renal hemodynamic responses to intravenous angiotensin II (Ang II, 30ââ?¬â??\n300 ng/kg/min) were tested under anesthesia, while renal perfusion pressure was held constant. The role of AT2R was examined\nby pretreating groups of rats with PD123319 or its vehicle. Renal blood flow (RBF) decreased in a dose-related manner in response\nto Ang II. Responses to Ang II were enhanced by pretreatment with estradiol. For example, at 300 ng kgâË?â??1 minâË?â??1, Ang II reduced\nRBF by 45.7 Ã?± 1.9% in estradiol-treated rats but only by 27.3 Ã?± 5.1% in vehicle-treated rats. Pretreatment with PD123319 blunted\nthe response of RBF to Ang II in estradiol-treated rats, so that reductions in RBF were similar to those in rats not treated with\nestradiol.We conclude that supraphysiological levels of estrogen promote AT2R-mediated renal vasoconstriction. This mechanism\ncould potentially contribute to the increased risk of cardiovascular disease associated with hormone replacement therapy using\nhigh-dose estrogen.
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