Testosterone‐Induced Vasorelaxation of Rat Mesenteric Microvasculature is Neuronal Nitric Oxide Synthase‐Dependent But Androgen Receptor‐Independent

Abstract

Recent studies reveal that testosterone (TES) produces rapid vasorelaxation of mesenteric arterioles at physiological concentrations; however, little is known about TES mechanisms in vascular smooth muscle (VSM). Therefore, acute mechanisms of TES were examined in endothelium‐intact rings of mesenteric arterioles (MA, 200 μm, dia.) prepared from male Sprague‐Dawley (SD) and Testicular‐feminized (Tfm; androgen receptor‐deficient) rats (14–18 wks age) for isometric tension using Halpern‐Mulvany myography. MA were precontracted with phenylephrine (20 μM) and a concen.‐response to TES was obtained (0.1–300 nM). Data are means+S.E (N = 3–13 rats). TES produced vasorelaxation at physiological concentrations in SD (50 ± 7%, EC50 = 2.3 ± 0.5 nM) and in Tfm (38 ± 5%, EC50 = 1.5 ± 0.5 nM). Pretreatment of Tfm MA with the neuronal NOS inhibitor LNPA (10 μM) nearly abolished TES effects (5.5 ± 3.8%). In SD VSM cells, TES activated the fluorescent nitric oxide (NO) indicator DAF‐2DA, while LNPA (10 μM) eliminated this effect of TES. These data suggest that: 1) TES exerts rapid vasorelaxing effects on VSM primarily through activation of nNOS and nitric oxide production; 2) TES‐induced vasorelaxation is a direct, nongenomic effect on VSM, independent of the cytosolic androgen receptor. (NIH: HL‐080402)