Nitric oxide and cGMP: mediators of pelvic nerve-stimulated erection in dogs

Trigo-Rocha, Flavio; Aronson, William J.; Hohenfellner, Markus; Ignarro, L. J.; Rajfer, Jacob; Lue, Tom F.

doi:10.1152/ajpheart.1993.264.2.h419

Cited by 53 publications

(38 citation statements)

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“…Furthermore, neurally activated tumescence is inhibited by a blockade of NO synthesis or the signal transduction cascade of NO (Burnett et al, 1992;Trigo-Rocha et al, 1993b;Hull et al, 1994). On the other hand, prolonging the activity of cyclic guanosine monophosphate, the second messenger activated by NO (Arnold et al, 1977) to cause relaxation of corporal smooth muscle (Ignarro et al, 1990), enhances pelvic nervestimulated penile erection (Trigo-Rocha et al, 1993a).…”

Section: Discussionmentioning

confidence: 99%

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

Chan

Huang²,

Chan³

1996

British J Pharmacology

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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.

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Section: Discussionmentioning

confidence: 99%

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

Chan

Huang²,

Chan³

1996

British J Pharmacology

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“…15,18 By contrast, the relaxant response to nitrergic nerve stimulation of isolated dog corpus cavernosum strips ceases rapidly after stimulation ends. 19 We speculated that the differential pattern of the responses in vitro and in vivo could be explained by the NO released from the sinusoidal endothelium as a result of stretching, which is due to the intracavernous pressure increase induced by neurogenic NO.…”

Section: Discussionmentioning

confidence: 99%

Characterization of nitrergic function in monkey penile erection in vivo and in vitro

et al. 2009

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The nitrergic nerve appears to have a major role in the neuronal regulation of penile erection. Cholinergic innervation has been shown histochemically in penile cavernous tissues, but its functional role is not well understood. This study was aimed at examining the functional properties of the nitrergic nerve and the possible involvement of cholinergic function in the regulation of monkey penile erection in vivo and in vitro. In anesthetized Japanese monkeys, electrical stimulation of the cavernous nerve caused a frequency-dependent increase in intracavernous pressure and penile erection, and atropine enhanced the pressure response. Intravenous injections of N G -nitro-L-arginine (L-NA) markedly inhibited the stimulation-induced pressure increase and the erectile response, and L-arginine partially restored the pressure response. In some monkeys, the intracavernous pressure increase caused by nerve stimulation was reversed by treatment with L-NA; however, L-arginine restored the pressor response. In addition, hexamethonium suppressed the pressure increase that resulted from the nerve stimulation. In corpus cavernosum isolated from monkeys, transmural electrical stimulation elicited frequency-dependent relaxation. The relaxation was attenuated by physostigmine, and was potentiated by atropine. Relaxation was markedly inhibited by treatment with L-NA. It appears that nitric oxide (NO) released from inhibitory nerves, even at low frequencies, has a pivotal role in the initiation and maintenance of intracavernous pressure increase and penile erection in monkeys. Prejunctional muscarinic receptors in nitrergic nerves are expected to participate in the impairment of NO release. Nitrergic nerves responsible for penile erection may originate from ganglia close to the corpus cavernosum. INTRODUCTIONThe function of nitric oxide (NO) as a neurotransmitter in nonadrenergic, noncholinergic nerves responsible for penile erection was first determined in the corpus cavernosum isolated from rabbits. 1 The presence of NO-synthase-containing nerve fibers in the corpora cavernosa and the involvement of NO in the intracavernous pressure increase by electrical stimulation of the cavernous nerve in anesthetized rats were outlined by Burnett et al. 2 The role of neurogenic NO in penile erection has been shown in a variety of experimental animals. [3][4][5] Involvement of the NO-cyclic GMP pathway in the relaxation of human corpus cavernosum strips in response to electrical field stimulation has also been shown. 6-9 Efficacy of phosphodiesterase-5 inhibitors in patients with erectile dysfunction supports the idea that cyclic GMP formed by NO-mediated activation of guanylyl cyclase has an important role in penile tumescence. 10 Recent studies suggest that NO released from the sinusoidal endothelium is also involved in the maintenance of penile erection. 11 Although cholinergic innervation has been shown in the penile corpus cavernosum, the functional role has not been elucidated. 12,13 Furthermore, reports in the literature have revealed...

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“…In dogs, intracavernous injection of zaprinast enhanced tumescence induced by pelvic nerve stimulation 5 and in human corpus cavernosum, zaprinast enhanced relaxations caused by electric ®eld stimulation or exogenously applied nitric oxide. 17 However, this was not con®rmed in rabbit erectile tissue since pretreatment with zaprinast did not signi®cantly augment the inhibitory effects of linsidamine (SIN-1), an NO donor. 24 In our study, amrinone, a potent cGMPinhibited PDE inhibitor, relaxed corpus cavernosum and the pD 2 values were similar to papaverine but the E m value was lower when compared with papaverine, sulmazole or zaprinast, thus con®rming previous reports.…”

Section: Effects Of the Speci®c Phosphodiesterase Inhibitors T Utkan mentioning

confidence: 98%

Effects of the specific phosphodiesterase inhibitors on alloxan-induced diabetic rabbit cavernous tissue in vitro

et al. 2001

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An experimental study was done to examine a potential role of phosphodiesterase (PDE) inhibitors in the treatment of diabetic erectile dysfunction. Relaxant effect of speci®c PDE inhibitors were measured in strips of corpus cavernosum smooth muscle taken from control and diabetic groups. Diabetes mellitus was induced in New Zealand white rabbits using alloxan. Penises excised from diabetic rabbits 8 weeks after the induction of diabetes mellitus. In the organ bath strips from control and diabetic rabbit corpus cavernosum were precontracted and increasing doses of several PDE inhibitors were added. In the precontracted rabbit cavernous tissue, sulmazole and zaprinast speci®c PDE V inhibitors were equally potent and ef®cacious in vitro but amrinone, a speci®c PDE III inhibitor, exhibits low relaxant effects. All PDE inhibitors tested showed a similar relaxation effect on corpus cavernosum smooth muscle from control and 8-week diabetic rabbits. The present study provides the possibility of using selective PDE III and V inhibitors in the treatment of diabetic impotence.

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Nitric oxide and cGMP: mediators of pelvic nerve-stimulated erection in dogs

Cited by 53 publications

References 0 publications

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

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

Characterization of nitrergic function in monkey penile erection in vivo and in vitro

Effects of the specific phosphodiesterase inhibitors on alloxan-induced diabetic rabbit cavernous tissue in vitro

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