Involvement Of Large-Conductance Ca(2+) -Activated K(+) Channels In Both Nitric Oxide And Endothelium-Derived Hyperpolarization-Type Relaxation In Human Penile Small Arteries.

Király, István Előd and Pataricza, János and Bajory, Zoltán and Simonsen, Ulf and Varró, András and Papp, Gyula and Pajor, László and Kun, Attila (2013) Involvement Of Large-Conductance Ca(2+) -Activated K(+) Channels In Both Nitric Oxide And Endothelium-Derived Hyperpolarization-Type Relaxation In Human Penile Small Arteries. BASIC & CLINICAL PHARMACOLOGY & TOXICOLOGY, 113 (1). pp. 19-24. ISSN 1742-7835

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Abstract

Large-conductance Ca(2+) -activated K(+) channels (BK(C) (a) ), located on the vascular smooth muscle, play an important role in regulation of vascular tone. In penile corpus cavernosum tissue, opening of BK(C) (a) channels leads to relaxation of corporal smooth muscle which is essential during erection; however, there is little information on the role of BK(C) (a) channels located in penile vascular smooth muscle. This study was designed to investigate the involvement of BK(C) (a) channels in endothelium-dependent and -independent relaxation of human intracavernous penile arteries. In human intracavernous arteries obtained in connection with transsexual operations, change of isometric force was recorded in microvascular myographs and endothelium-dependent (nitric oxide (NO) and endothelium-derived hyperpolarization (EDH)-type) and -independent (NO-donor) relaxation was measured in contracted arteries. In penile small arteries contracted with phenylephrine, acetylcholine evoked NO- and EDH-type relaxations which were sensitive to iberiotoxin, a selective blocker of BK(C) (a) channels. Iberiotoxin also inhibited relaxations induced by a NO donor, sodium nitroprusside. NS11021, a selective opener of BK(C) (a) channels, evoked pronounced relaxations which were inhibited in the presence of iberiotoxin. NS13558, a BK(C) (a) inactive analogue of NS11021, failed to relax human penile small arteries. Our results show that BK(C) (a) channels are involved in both NO- and EDH-type relaxation of intracavernous penile arteries obtained from healthy men. The effect of a selective opener of BK(C) (a) channels also suggests that direct activation of the channel may be an advantageous approach for treatment of impaired endothelium-dependent relaxation often associated with erectile dysfunction.

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