Possible role of Ca2+ channels in the vasodilating effect of 5ß-dihydrotestosterone in rat aorta
Por:
Perusquía M., Villalón C.M.
Publicada:
1 ene 1999
Resumen:
It has previously been shown that the androgen, 5?-dihydrotestosterone (17?-hydroxy-5?-androstan-3-one, 5?-DHT), is able to produce an endothelium-independent vasodilating effect in rat aorta. The present study analyzed the mechanisms underlying the above vasodilator effect of 5?-dihydrotestosterone, with particular emphasis on verifying a possible interaction with GABA(A) receptors, ?-adrenoceptors and Ca2+ channels. Rat aortic rings without endothelium were isometrically recorded. 5?-Dihydrotestosterone produced a concentration-dependent relaxation on the contractions induced by noradrenaline (NA; 0.3 ?M) or K+ (KCl; 60 mM), with the latter being more sensitive to 5?-dihydrotestosterone-induced relaxation than the former; the concentration-response curves showed that 5?-dihydrotestosterone is significantly more potent than 17?-estradiol (1,3,5(10)-estratrien-3,17?-diol) to induce vasodilatation. The vasodilating effect of 5?-dihydrotestosterone on noradrenaline-induced contraction was resistant to blockade by the GABA(A) receptor antagonists, picrotoxin or bicuculline, and the ?-adrenoceptor antagonist, propranolol, a finding that excludes an interaction of the steroid with GABA(A) receptors and ?-adrenoceptors. Interestingly, the contractions evoked by calcium in depolarized tissues were substantially inhibited by 5?-dihydrotestosterone, implying that this steroid could be an endogenous calcium channel blocker; consistent with this finding, 5?-dihydrotestosterone was able to relax tissues precontracted with the calcium channel opener, Bay K 8644. Moreover, although the rings precontracted with noradrenaline and potassium were almost equipotently relaxed by 5?-dihydrotestosterone. Nifedipine was more potent than 5?-dihydrotestosterone to block the potassium-induced contraction, but the steroid was more effective than nifedipine to prevent noradrenaline-induced contraction. The above results suggest that 5?-dihydrotestosterone causes relaxation of rat aorta by acting directly on the membrane of smooth muscle cells; this non-genomic action may be explained in terms of a blockade of voltage- and receptor-dependent calcium channels, a mechanism that restricts the availability of extracellular calcium in the contractile machinery. Copyright (C) 1999 Elsevier Science B.V.
Filiaciones:
Perusquía M.:
Univ. Nac. Auton. de Mexico, Inst. Invest. Biomed., Apdo. P., Mexico City, Mexico
Villalón C.M.:
Secc. de Terap. Experimental, Depto. Farmacol., CINVESTAV, I.P.N., Mexico City, Mexico
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