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

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Abstract
1 . The effect of local application of cocaine to the corpus cavemosum on intracavemous 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 . Intracavemous (i.e.) administration of cocaine (40, 80 or 160 μg) to the corpus cavemosum resulted in a dose-related increase in both amplitude and duration of ICP. 3 . The elevation in ICP induced by cocaine (160 μg, i.e.) was not significantly influenced by prior injection into the corpus cavemosum of either the D1 or D2 dopamine receptor antagonist, R-(+)-SCH 23390 (250 pmol) or (—)-sulpiride (250 pmol). 4 . Similarly, penile erection promoted by cocaine (160 μg, i.e.) was not appreciably affected by i.e. pretreatment with the α1, α2-, or β-adrenoceptor antagonist, prazosin (50 pmol), yohimbine (50 pmol) or propranolol (5 nmol). 5 . Whereas lignocaine (4 μmol, i.e.) depressed penile erection induced by papaverine (400 μg, i.e.), local application of cocaine (160 μg) into the corpus cavemosum still elicited significant elevation in ICP in the presence of lignocaine or papaverine. 6 . The increase in ICP induced by cocaine (160 μg, i.e.) was attenuated dose-dependently by prior cavemosal administration of the NO synthase inhibitor, Nω-nitro-L-arginine methyl ester (1-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.e.). 7 . Pretreatment by local application into the corpus cavemosum of methylene blue (2.5 μmol), an inhibitor of cytosolic guanylyl cyclase, antagonized cocaine-induced penile erection. 8 . Direct i.e. 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 cavemosum. 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 cavemosal application of cocaine engaged an active participation of NO and subsequent activation of guanylyl cyclase in the corpus cavemosum.