Mechanisms underlying endothelium-dependent, nitric oxide/prostacyclin-independent, acetylcholine-induced relaxation in canine corpus cavernosum.

Abstract

The mechanisms underlying endothelium-dependent and nitric oxide (NO)/prostacyclin-independent, acetylcholine-induced relaxation in isolated canine corpus cavernosum were investigated. In isolated canine corpus cavernous strips treated with indomethacin (10(-6) M) and N(G)-nitro-L-arginine (10(-4) M), acetylcholine produced relaxations in a concentration-dependent manner. The relaxations were not affected by treatment with 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazole-1-oxyl 3-oxide, sodium salt (carboxy PTIO, 3 x 10(-4) M), glibenclamide (10(-6) M), iberiotoxin (10(-7) M) or charybdotoxin (10(-7) M), but were abolished or reversed to contractions by treatment with apamin (10(-8) M) or scyllatoxin (10(-8) M). Levcromakalim (10(-7)-10(-6) M) induced a concentration-dependent relaxation which was abolished by treatment with glibenclamide (10(-6) M), but was not affected by treatment with apamin (10(-8) M) or scyllatoxin (10(-8) M). These findings indicate that endothelial cells of canine corpus cavernosum have an ability to produce a relaxing substance(s) other than NO or prostacyclin in response to acetylcholine. The substance(s) may open solely small conductance Ca2+-dependent K+ channels.