Hypotestosteronemia‐Induced Hypertension in Male Sprague‐Dawley Rats is Reversed by Testosterone Replacement Therapy, Which is a Non‐Genomic, Estrogen‐Independent Effect

Abstract

Acutely, testosterone (TES) and other androgens are efficacious vasodilators, both in vitro and in vivo; however, their long‐term effects on arterial blood pressure (BP) are unclear. We previously reported that castration (CsX) produced hypertension in male rats, and that TES replacement therapy (TRT) was antihypertensive and normalized BP via inhibition of renin‐angiotensin system function. Thus, long‐term effects of endogenous TES and exogenous TRT on BP were studied in male Sprague‐Dawley (SD) and Testicular‐feminized male (Tfm, androgen receptor defective) rats. 12–13 wk old male rats were castrated (CsX) and weekly measurements of systolic BP (tail cuff plethysmography) revealed a progressive rise in BP over 10 wks in CsX‐SD (109.5 ± 1.3 vs. 139.1 ± 0.4 mmHg) and in CsX‐Tfm (108 ± 0.9 vs. 138.4 ± 0.3 mmHg). During the next 5 weeks, TRT with 5α‐dihydro‐TES‐enanthate (1.00 mg/kg 2X/wk) gradually reduced BP to normal in CsX‐SD rats (111.4 ± 1). TRT of CsX‐Tfm rats over 5 weeks with TES‐enanthate (1.75 mg/kg 2X/wk) reduced BP to a similar extent. 24 hr urine output (UO) in intact SD was 48.3 ml/kg at baseline, 34.3 at 10 wks, 38.4 at 12 wks, and 34.8 at 15 wks. UO in CsX‐SD was 47.6, 30.3, 25.2, and 27.7; UO in CsX+TRT was 46.1, 29.2 36.2, and 29.5. Plasma TES in SD rats (radioimmunoassay, RIA) was 0.40 ng/ml in intact rats, <0.1 ng/ml in CsX, and 1.05 ng/ml in CsX+TRT. Plasma estrogen in SD (RIA) was 15.1 pg/ml in intact rats, 15.2 in CsX, and 15.4 in CsX+TRT. These data suggest that: 1) TES exerts antihypertensive effects in male SD and Tfm rats; 2) the antihypertensive effect of TES appear to involve a diuretic effect on the kidney, which is non‐genomically mediated and independent of TES aromatization to estrogen. (State of Texas).Support or Funding InformationState of TexasThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.