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RENAL HEMODYNAMICS AND CARDIORENAL INTEGRATION
Basic Biomedical Sciences, University of South Dakota, Vermillion, South Dakota
Submitted 24 May 2005 ; accepted in final form 29 January 2006
Males develop higher blood pressure than do females. This study tested the hypothesis that androgens enhance responsiveness to ANG II during the development of hypertension in New Zealand genetically hypertensive (NZGH) rats. Male NZGH rats were obtained at 5 wk of age and subjected to sham operation (Sham) or castration (Cas) then studied at three age groups: 67, 1112, and 1617 wk. Mean arterial blood pressure (MAP), heart rate (HR), and renal blood flow (RBF) measurements were recorded under Inactin anesthesia. These variables were measured after enalapril (1 mg/kg) treatment and during intravenous ANG II infusion (20, 40, and 80 ng/kg/min). Plasma testosterone was measured by ELISA. Angiotensin type 1 (AT1) receptor expression was assessed by Western blot analysis and RT-PCR. ANG II-induced MAP responses were significantly attenuated in Cas NZGH rats. At the highest ANG II dose, MAP increased by 40 ± 4% in Sham vs. 22 ± 1% in Cas NZGH rats of 1617 wk of age. Similarly, renal vascular resistance (RVR) responses to ANG II were reduced by castration (209 ± 20% in Sham vs. 168 ± 10% in Cas NZGH rats at 1617 wk of age). Castration also reduced MAP recorded in conscious NZGH rats of this age group. Testosterone replacement restored baseline MAP and the pressor and RVR responses to ANG II. Castration reduced testosterone concentrations markedly. Testosterone treatment restored these concentrations. Neither castration nor castration+testosterone treatment affected AT1 receptor mRNA or protein expression. Collectively, these data suggest that androgens modulate renal and systemic vascular responsiveness to ANG II, which may contribute to androgen-induced facilitation of NZGH rat hypertension.
angiotensin; sex steroids; kidney; hypertension
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