Hypotestosteronemia‐induced hypertension in male Sprague‐Dawley rats is renin‐ angiotensin system‐dependent

Abstract

Acutely, testosterone (TES) and other androgens are efficacious vasodilators, both in vitro and in vivo; however, long‐term effects of the androgens on arterial blood pressure (BP) are unclear. Thus, long‐term effects of endogenous and exogenous TES on BP were studied in male Sprague‐ Dawley rats. 12–13 wk old rats remained intact (InT) or were castrated (CsX). Weekly measurements of systolic BP (tail cuff plethysmography) revealed a progressive rise in BP over 10 wks in CsX (108 ± 0.9 vs. 139 ± 2 mmHg), while BP remained stable in InT (109 ± 3 vs. 113 ± 0.3). During the next 5 weeks, half of the CsX received TES replacement therapy (CsX+TES‐ enanthate‐replaced; 1.75 mg/kg, given 2X/wk). BP gradually declined to normal in CsX+TES replaced rats (118 ± 1), while BP remained elevated in CsX (141 ± 1) and normal in InT (112 ± 3). Seminal vesicle and body weights of InT (1.212 ± 0.038 g and 441 ± 9 g, respectively), CsX (0.065 ± 0.006 g and 420 ± 4 g) and CsX+TES (1.203 ± 0.080 g and 433 ± 3 g) revealed that TES replacement produced physiological levels of TES. In a separate group of CsX rats, treatment with Losartan (LST; 250 mg/L drinking water) prevented development of hypertension at 10 wks (94 ± 2 CsX+LST vs. 131 ± 3 CsX). During the next 5 weeks with TES replacement therapy, BP declined in CsX+TES (114 ± 2) and remained lower in CsX+LST (101 ± 1). These data suggest that: 1) endogenous androgens (TES) exert antihypertensive effects in male SD rats; and 2) these antihypertensive effects may involve TES‐induced reductions in renin‐ angiotensin system function. (State of Texas)