NITRIC-OXIDE AS A MEDIATOR OF COCAINE-INDUCED PENILE ERECTION IN THE RAT

1 The effect of local application of cocaine to the corpus cavernosum on intracavernous pressure (ICP), an experimental index for penile ere ction, was examined in Sprague-Dawley rats anaesthetized with chloral hydrate. The potential involvement of dopamine, noradrenaline or nitri c oxide as the chemical mediator in this process, and the pharmacologi cal action of cocaine as a local anaesthetic in the induced increase i n ICP, were also investigated. 2 Intracavernous (i.c.) administration of cocaine (40, 80 or 160 mu g) to the corpus cavernosum resulted in a dose-related increase in both amplitude and duration of ICP. 3 The el evation in ICP induced by cocaine (160 mu g, i.c.) was not significant ly 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 b y cocaine (160 mu g,i.c.) was not appreciably affected by i.c. pretrea tment with the alpha(1)-, alpha(2)-, or beta-adrenoceptor antagonist, prazosin (50 pmol), yohimbine (50 pmol) or propranolol (5 nmol). 5 Whe reas lignocaine (4 mu mol, i.c.) depressed penile erection induced by papaverine (400 mu g, i.c.), local application of cocaine (160 mu g) i nto the corpus cavernosum still elicited significant elevation in ICP in the presence of lignocaine or papaverine. 6 The increase in ICP ind uced by cocaine (160 mu g, i.c.) was attenuated dose-dependently by pr ior cavernosal administration of the NO synthase inhibitor, N-omega-ni tro-L-arginine methyl ester (L-NAME, 0.5, 1 or 5 pmol) or NG-monomethy l-L-arginine (L-NMMA, 2.5, 5 or 10 pmol). The blunting effect of L-NAM E or L-NMMA was reversed by co-administration of the NO precursor, L-a rginine (1 nmol, i.c.). 7 Pretreatment by local application into the c orpus cavernosum of methylene blue (2.5 mu mol), an inhibitor of cytos olic guanylyl cyclase, antagonized cocaine-induced penile erection. 8 Direct i.c. administration of a NO donor, nitroglycerin (10 or 20 nmol ), mimicked the local action of cocaine by promoting a significant inc rease in ICP. 9 It is concluded that cocaine may induce penile erectio n by increasing ICP via a local action on the corpus cavernosum This p rocess did not appear to involve either dopamine or noradrenaline as t he chemical mediator, nor the pharmacological action of cocaine as a l ocal anaesthetic. On the other hand, it is likely that initiation and maintenance of penile erection elicited by cavernosal application of c ocaine engaged an active participation of NO and subsequent activation of guanylyl cyclase in the corpus cavernosum.