3β‐Diol, an endogenous androgen, elicits relaxation via estrogen receptor activation in rat mesenteric and cerebral arteries (1156.15)

Nongenomic vasorelaxant effects of androgens, such as testosterone and dihydrotestosterone (DHT), have been shown to be beneficial in a variety of vascular beds. These nongenomic vasorelaxant actions have been shown to be independent of androgen receptor (AR) activation. However, the vascular properties and associated mechanisms for endogenous androgen metabolites downstream of these potent AR agonists have not been investigated. Therefore, we studied the direct vasorelaxing effects of the endogenous DHT metabolite, 5α‐androstane 3β, 17β diol (3β‐diol), on contracted mesenteric and basilar arterial rings isolated from male rats via wire myography. Previous studies have demonstrated that the actions of 3β‐diol are mediated by estrogen receptor beta (ERβ). Thus, we confirmed the presence of ERβ expression along with AR and ERα in mesenteric and cerebral arteries using western blot and RT‐PCR. In the contractile studies, 3β‐diol (10 ‐9 to 10 ‐5 M) reduced phenylephrine‐induced contractions in mesenteric rings. Similarly, serotonin‐induced contractions in basilar rings were also reduced by the addition of 3β‐diol (10 ‐9 to 10 ‐5 M). Vasorelaxing efficacy for 3β‐diol was greater in mesenteric rings (R max = 77.34%±17.05) compared to basilar rings (R max = 65.92% ±7.74). In both mesenteric and basilar arteries, non‐selective ER inhibition with ICI 182780 and selective ERβ inhibition with PHTPP attenuated 3β‐diol relaxation compared to vehicle. Based on these findings it is concluded that 1) the endogenous androgen metabolite, 3β‐diol, mediates direct vasorelaxation of arterial rings via ERβ and 2) regional differences in vasorelaxation of 3β‐diol exist between the peripheral and cerebral circulations. Grant Funding Source : Supported by the UA Sarver Heart Center