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Advances in Pharmacological Sciences
Volume 2015 (2015), Article ID 682745, 7 pages
Research Article

High-Dose Estradiol-Replacement Therapy Enhances the Renal Vascular Response to Angiotensin II via an AT2-Receptor Dependent Mechanism

1Department of Physiology, Zahedan University of Medical Sciences, Isfahan, Iran
2Water & Electrolytes Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
3Department of Physiology, Isfahan University of Medical Sciences, Isfahan, Iran
4Isfahan MN Institute of Basic & Applied Sciences Research, Isfahan, Iran
5Department of Physiology, Monash University, Clayton, VIC, Australia

Received 14 September 2015; Accepted 5 November 2015

Academic Editor: Todd C. Skaar

Copyright © 2015 Tahereh Safari et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


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