Penile erection in the primate: induction with nitric-oxide donors.
The primate model has been used for investigations on the physiology and pharmacology of erection. Recent in vitro investigations indicate that nitric oxide acts as the mediator of penile erection, but in vivo primate studies are needed to corroborate these findings. Penile erections were induced in a primate model using intracavernosal injections of nitric oxide donors s-nitrocysteine (NO-CYS) and sodium nitroprusside (SNP), and acetylcholine (ACh) which stimulates the formation of nitric oxide. Penile length and intracavernosal pressures following agonist injection were compared with baseline (flaccid) and control erections (elicited by injection of a papaverine/phentolamine/PGE1 standard mixture). Dose-response curves for each drug were determined with respect to maximal intracavernosal pressure, duration of effect and penile length, and systemic arterial pressure was monitored. All three agents induced erections, with dose-dependent increases in cavernosal pressure and penile length. The maximal cavernosal pressure attained was similar for all three agents, but the duration of action was significantly shorter with ACh (p < .05). Injection of L-nitro-arginine-methyl-ester (L-NAME), a nitric oxide synthase inhibitor, before injection of the nitric oxide donor shortened the duration of effect but did not alter maximal cavernosal pressure or penile length attained. Although systemic hypotension was induced by each agent, digital compression at the base of the penis at the time of injection prevented such changes. These results suggest that the primate is a useful model to evaluate the action of substances that induce or inhibit penile erection. The findings provide support for the hypothesis that nitric oxide is a mediator of penile erection and that nitric oxide donors may be useful in the treatment of erectile dysfunction.
Hellstrom
W J
WJ
Department of Urology, Tulane University School of Medicine, New Orleans, Louisiana 70112-2699.
Monga
M
M
Wang
R
R
Domer
F R
FR
Kadowitz
P J
PJ
Roberts
J A
JA
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D003545:Cysteine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D008252:Macaca fascicularis; D008297:Male; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000378:metabolism; D009599:Nitroprusside / Q000494:pharmacology*; D010410:Penile Erection / Q000187:drug effects*; D026403:S-Nitrosothiols
D026403:S-Nitrosothiols; D009599:Nitroprusside; D009569:Nitric Oxide; C021315:S-nitrosocysteine; D001120:Arginine; D003545:Cysteine; D000109:Acetylcholine; D019331:NG-Nitroarginine Methyl Ester