Phentolamine relaxes human corpus cavernosum by a nonadrenergic mechanism activating ATP-sensitive K+ channel.

To investigate the pharmacodynamics of phentolamine in human corpus cavernosum (HCC) with special attention to the role of the K+ channels. Strips of HCC precontracted with nonadrenergic stimuli and kept in isometric organ bath immersed in a modified Krebs-Henseleit solution enriched with guanethidine and indomethacine were used in order to study the mechanism of the phentolamine-induced relaxation. Phentolamine caused relaxation (˜50%) in HCC strips precontracted with K+ 40?mM. This effect was not blocked by tetrodotoxin (1?µM) (54.6±4.6 vs 48.9±6.4%) or (atropine (10?µM) (52.7±6.5 vs 58.6±5.6%). However, this relaxation was significantly attenuated by L-NAME (100?µM) (59.7±5.8 vs 27.8±7.1%; P<0.05; n=8) and ODQ (100?µM) (62.7±5.1 vs 26.8±3.9%; P<0.05; n=8). Charybdotoxin and apamin (KCa-channel blockers) did not affect the phentolamine relaxations (54.6±4.6 vs 59.3±5.2%). Glibenclamide (100?µM), an inhibitor of KATP-channel, caused a significant inhibition (56.7±6.3 vs 11.3±2.3%; P<0.05; n=8) of the phentolamine-induced relaxation. In addition, the association of glibenclamide and L-NAME almost abolished the phentolamine-mediated relaxation (54.6±5.6 vs 5.7±1.4%; P<0.05; n=8). The results suggest that phentolamine relaxes HCC by a nonadrenergic-noncholinergic mechanism dependent on nitric oxide synthase activity and activation of KATP-channel.International Journal of Impotence Research (2005) 17, 27-32. doi:10.1038/sj.ijir.3901269 Published online 28 October 2004 [ABSTRACT FROM AUTHOR]