title: Involvement of large-conductance Ca(2+) -activated K(+) channels in both nitric oxide and endothelium-derived hyperpolarization-type relaxation in human penile small arteries.
abstract: Large-conductance Ca(2+) -activated K(+) channels (BKC a ), located on the vascular smooth muscle, play an important role in regulation of vascular tone. In penile corpus cavernosum tissue, opening of BKC a channels leads to relaxation of corporal smooth muscle, which is essential during erection; however, there is little information on the role of BKC a channels located in penile vascular smooth muscle. This study was designed to investigate the involvement of BKC a channels in endothelium-dependent and endothelium-independent relaxation of human intracavernous penile arteries. In human intracavernous arteries obtained in connection with transsexual operations, change in isometric force was recorded in microvascular myographs, and endothelium-dependent [nitric oxide (NO) and endothelium-derived hyperpolarization (EDH)-type] and endothelium-independent (NO-donor) relaxations were measured in contracted arteries. In penile small arteries contracted with phenylephrine, acetylcholine evoked NO- and EDH-type relaxations, which were sensitive to iberiotoxin (IbTX), a selective blocker of BKC a channels. Iberiotoxin also inhibited relaxations induced by a NO-donor, sodium nitroprusside. NS11021, a selective opener of BKC a channels, evoked pronounced relaxations that were inhibited in the presence of IbTX. NS13558, a BKC a -inactive analogue of NS11021, failed to relax human penile small arteries. Our results show that BKC 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 BKC 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.
authors: Department of Urology, University of Szeged, Szeged, Hungary.
authors: István
authors: I
authors: Király
authors: János
authors: J
authors: Pataricza
authors: Zoltán
authors: Z
authors: Bajory
authors: Ulf
authors: U
authors: Simonsen
authors: András
authors: A
authors: Varro
authors: Julius Gy
authors: JG
authors: Papp
authors: Lászlo
authors: L
authors: Pajor
authors: Attila
authors: A
authors: Kun
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000293:Adolescent; D000328:Adult; D001158:Arteries / Q000378:metabolism*; D004727:Endothelium / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000378:metabolism*; D008297:Male; D009126:Muscle Relaxation / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D009569:Nitric Oxide / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D010413:Penis / Q000098:blood supply*; D010455:Peptides / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D013777:Tetrazoles / Q000494:pharmacology; D013890:Thiourea / Q000031:analogs & derivatives / Q000494:pharmacology; D055815:Young Adult
chemical_list: C524410:1-(3,5-bis(trifluoromethyl)phenyl)-3-(4-bromo-2-(1H-tetrazol-5-yl)phenyl)thiourea; D051036:Large-Conductance Calcium-Activated Potassium Channels; C550411:NS13558; D010455:Peptides; D013777:Tetrazoles; D009599:Nitroprusside; D010656:Phenylephrine; D009569:Nitric Oxide; C064719:iberiotoxin; D013890:Thiourea; D000109:Acetylcholine