Nitric oxide as a mediator of cocaine-induced penile erection in the rat

摘要

1. The effect of local application of cocaine to the corpus cavernosum on intracavernous pressure (ICP), an experimental index for penile erection, was examined in Sprague-Dawley rats anaesthetized with chloral hydrate. The potential involvement of dopamine, noradrenaline or nitric oxide as the chemical mediator in this process, and the pharmacological action of cocaine as a local anaesthetic in the induced increase in ICP, were also investigated. 2. Intracavernous (i.c.) administration of cocaine (40, 80 or 160 μg) to the corpus cavernosum resulted in a dose-related increase in both amplitude and duration of ICP. 3. The elevation in ICP induced by cocaine (160 μg, i.c.) was not significantly influenced by prior injection into the corpus cavernosum of either the D_1 or D_2 dopamine receptor antagonist, R-( + )-SCH 23390 (250 pmol) or (-)-sulpiride (250 pmol). 4. Similarly, penile erection promoted by cocaine (160 μg, i.c.) was not appreciably affected by i.c. pretreatment with the 羅1, α_2, or β-adrenoceptor antagonist, prazosin (50 pmol), yohimbine (50 pmol) or propranolol (5 nmol). 5. Whereas lignocaine (4 μmol, i.c.) depressed penile erection induced by papaverine (400 μg, i.c.), local application of cocaine (160 μg) into the corpus cavernosum still elicited significant elevation in ICP in the presence of lignocaine or papaverine. 6. The increase in ICP induced by cocaine (160 μg, i.c.) was attenuated dose-dependently by prior cavernosal administration of the NO synthase inhibitor, N~ω-nitro-L-arginine methyl ester (L-NAME, 0.5, 1 or 5 pmol) or NG-monomethyl-L-arginine (L-NMMA, 2.5, 5 or 10 pmol). The blunting effect of L-NAME or L-NMMA was reversed by co-administration of the NO precursor, L-arginine (1 nmol, i.c.).