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

Abstract

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. Whereas lignocaine (4 pmol, i.c.) depressed penile erection induced by papaverine (400 gg, i.c.), local application of cocaine (160 pg) 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 Mg, i.c.) was attenuated dose-dependently by prior cavernosal administration of the NO synthase inhibitor, Nw-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.). 7 Pretreatment by local application into the corpus cavernosum of methylene blue (2.5 ,mol), an inhibitor of cytosolic 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 increase in ICP. 9 It is concluded that cocaine may induce penile erection by increasing ICP via a local action on the corpus cavernosum. This process did not appear to involve either dopamine or noradrenaline as the chemical mediator, nor the pharmacological action of cocaine as a local anaesthetic. On the other hand, it is likely that initiation and maintenance of penile erection elicited by cavernosal application of cocaine engaged an active participation of NO and subsequent activation of guanylyl cyclase in the corpus cavernosum.

Priapism Associated with Intracavernosal Injection of Cocaine

“…Substances which are inhibitors of guanylate cyclase like methylene blue can thus inhibit the conversion of GTP to cGMP and thus inhibit erection at the local level [11]. It is believed this explains the finding as outlined here.…”

“…Some of these substances include cocaine [11]. Once NO is released, it then acts on guanylate cyclase in the conversion of GTP to cGMP.…”

Nitric Oxide Agents and Apomorphine-Induced Rat Behaviors

“…However, its response was not altered by L-arginine. While apomor-phine-induced penile erection may be mediated centrally [26], the response of NO seems to be due to a peripheral mechanism [31]. Our data indicate that L-NAME (10 mg/ kg) also increased apomorphine-induced penile erection.…”

Hippocampal noradrenergic neurotransmission in concurrent EEG desynchronization and inhibition of penile erection induced by cocaine in the rat

“…The increase in intracavernous pressure (ICP) was used as our experimental index for penile erection ( Chen et al ., 1992 ). As reported previously ( Chen et al ., 1992 ; Chan et al ., 1996 ; Chang et al ., 1998a , 1998b ), the lower part of the body was rotated slightly to provide adequate exposure of the genital area. The skin overlying the penis was incised, and the prepuce was degloved to fully expose both corpora cavernosa.…”