Pharmacological evidence that Ca(2+) channels and, to a lesser extent, K(+) channels mediate the relaxation of testosterone in the canine basilar artery

Testosterone induces vasorelaxation through non-genomic mechanisms in several isolated blood vessels, but no study has reported its effects on the canine basilar artery, an important artery implicated in cerebral vasospasm. Hence, this study has investigated the mechanisms involved in testosterone-induced relaxation of the canine basilar artery. For this purpose, the vasorelaxant effects of testosterone were evaluated in KCl- and/or PGF(2 alpha)-precontracted arterial rings in vitro in the absence or presence of several antagonists/inhibitors/blockers; the effect of testosterone on the contractile responses to CaCl(2) was also determined. Testosterone (10-180 mu M) produced concentration-dependent relaxations of KCl- or PGF(2 alpha)-precontracted arterial rings which were: (i) unaffected by flutamide (10 mu M), DL-aminoglutethimide (10 mu M), actinomycin D (10 mu M), cycloheximide (10 mu M), SQ 22,536 (100 mu M) or ODQ(30 mu M); and (ii) significantly attenuated by the blockers 4-aminopyridine (K(V); 1 mM), BaCl(2) (K(IR); 30 mu M), iberiotoxin (BK(Cd2+); 20 nM), but not by glybenclamide (K(ATP); 10 mu M). In addition, testosterone (31, 56 and 180 mu M) and nifedipine (0.01-1 mu M) produced a concentration-dependent blockade of the contraction to CaCl(2) (10 mu M to 10 mM) in arterial rings depolarized by 60 mM KCl. These results, taken together, show that testosterone relaxes the canine basilar artery mainly by blockade of voltage-dependent Ca(2+) channels and, to a lesser extent, by activation of K(+) channels (K(IR), K(V) and BK(Ca2+)). This effect does not involve genomic mechanisms, production of cAMP/cGMP or the conversion of testosterone to 17 beta-estradiol. (C) 2010 Elsevier Inc. All rights reserved.