Mechanisms of vasorelaxation to testosterone in the rat aorta

We have investigated the role of endothelium-derived relaxing factors, K+ channels and steroid receptors in vasorelaxation to testosterone in the rat aorta. Testosterone (1 nM-mM) caused acute concentration-dependent vasorelaxation. Both indomethacin (10 muM) and flurbiprofen (10 muM) uncovered relaxant responses to testosterone. The action of indomethacin was inhibited by endothelial removal. N-G-nitro-L-arginine methyl ester (L-NAME, 300 muM) had no effects on testosterone-induced responses. In the presence of indomethacin, the vasorelaxant potency of testosterone was reduced by depolarization with 60 mM KCl or charybdotoxin (100 nM), but not by glibenclamide (10 muM), 4-ammopyridine (1 mM) or barium chloride (30 muM). The responses to testosterone were not inhibited by flutamide (10 muM) or mifepristone (30 muM). Pre-treatment of the aorta with testosterone (100 muM) inhibited CaCl-induced contraction. In the present study, we have demonstrated that testosterone causes acute vasorelaxations, which are modulated via endothelium-derived prostanoids. The responses uncovered by cyclooxygenase inhibitors are due to the activation of K-Ca channels, while at higher concentrations, testosterone inhibits Ca2+ influx. (C) 2003 Elsevier Science B.V. All rights reserved.