Systemic hypotensive effects of testosterone are androgen structure-specific and neuronal nitric oxide synthase-dependent. Academic Article uri icon


  • Testosterone (TES) and other androgens exert a direct vasorelaxing action on the vasculature in vitro that is structurally specific and independent of cytosolic androgen receptor (AR). The effects of intravenous androgen infusions on mean arterial blood pressure (BP) and heart rate (HR) were determined in conscious, unrestrained, chronically catheterized, ganglionically blocked (hexamethonium, HEX; 30 mg/kg ip) male Sprague-Dawley (SD) and testicular-feminized male (Tfm; AR-deficient) rats, 16-20 wk of age. BP and HR were recorded at baseline and with increasing doses of androgens (0.375-6.00 molkg(-1)min(-1) iv; 10 min/dose). Data are expressed as means SE (n = 5-8 rats/group). In SD rats, baseline BP and HR averaged 103 4 mmHg and 353 12 beats/min (bpm). TES produced a dose-dependent reduction in BP to a low of 87 4 mmHg (16%), while HR was unchanged (354 14 bpm). Neither BP (109 3 mmHg) nor HR (395 13 bpm) were altered by vehicle (10% EtOH in 0.9% saline; 0.15 mlkg(-1)min(-1), iv). In Tfm, TES produced a similar reduction in BP (99 3 to 86 3 mmHg, 13%); HR was unchanged (369 18 bpm). In SD, 5-dihydrotestosterone (genomically inactive metabolite) produced a greater reduction in BP than TES (102 2 to 79 2 mmHg, 23%); HR was unchanged (361 9). A 20-g iv bolus of sodium nitroprusside in both SD and Tfm rats reduced BP 30-40 mmHg, while HR was unchanged, confirming blockade by HEX. Pretreatment of SD rats with neuronal nitric oxide synthase (nNOS) inhibitor (S-methyl-thiocitrulline, SMTC; 20 gkg(-1)min(-1) 30 min) abolished the hypotensive effects of TES infusion on BP (104 2 vs. 101 2 mmHg) and HR (326 11 vs. 324 8 bpm). These data suggest the systemic hypotensive effect of TES and other androgens involves a direct vasodilatory action on the peripheral vasculature which, like the effect observed in isolated arteries, is structurally specific and AR-independent, and involves activation of nNOS.

published proceedings

  • Am J Physiol Regul Integr Comp Physiol

altmetric score

  • 1

author list (cited authors)

  • Perusqua, M., Greenway, C. D., Perkins, L. M., & Stallone, J. N.

citation count

  • 22

complete list of authors

  • Perusquía, Mercedes||Greenway, Clayton D||Perkins, Lisa M||Stallone, John N

publication date

  • January 2015