The modulatory role of androgens and progestins in the induction of vasorelaxation in human umbilical artery

Sex steroids have been described as protectors of the cardiovascular system and one of their relevant actions is inhibition of vascular tone. However, this information has been derived from animal models. The aim of this study was to investigate the vasorelaxant properties of several progestins and androgens on the vascular tone of human umbilical artery (HUA) to elucidate their potential regulatory role on fetoplacental blood flow. HUA rings, obtained from umbilical cords at vaginal deliveries and cesarean section from term uncomplicated pregnancies, were isometrically recorded and precontracted with either KCl or serotonin. Subsequently, dehydroepiandrosterone, testosterone, progesterone and some of their 5-reduced metabolites were added at different noncumulative concentrations on KCl-induced precontraction. There were significant differences in the vasorelaxing responses to these steroids; excluding 5α-pregnandione, the remaining steroids induced concentration-dependent vasorelaxations. In general, androgens were more potent than progestins, with 5β-dihydrotestosterone being the most potent one. These vasorelaxations remained unaffected by inhibitors of transcription and translation, selective steroid receptor antagonists, a nitric oxide synthase inhibitor or specific blockers of K+ channels. Interestingly, the serotonin contraction was significantly less sensitive to steroid-induced vasorelaxation. Moreover, the contraction evoked by Ca2+ in depolarized tissues (by KCl–Ca2+ free solution) was prevented by steroids. These data, taken together, suggest that sex steroids (particularly androgens) induce an acute (nongenomically-mediated) vasorelaxing effect on the HUA which may be mediated by: (i) a nitric oxide-independent pathway; and/or (ii) a decrease in external Ca2+ influx by inactivating Ca2+ channels, but not by activating K+ channels.