Cyclic guanosine monophosphate mediates penile erection in the rat.
Recent in vivo and in vitro studies suggest that nitric oxide or a nitric-oxide-like substance mediates nonadrenergic, noncholinergic relaxation of trabecular smooth muscle through activation of the cyclic guanosine monophosphate (cGMP) pathway. In 60 Sprague-Dawley rats, we investigated the effect of intracavernous administration of different drugs known to act at different levels of the cyclic adenosine monophosphate (cAMP) and cGMP pathways. Neither cAMP nor drugs that stimulate adenylate cyclase activity (vasoactive intestinal peptide, prostaglandin E1, calcitonin gene-related peptide) provoked any change in the basal intracavernous pressure. N-ethylmaleimide, an inhibitor of the enzyme adenylate cyclase, did not modify the response to electrostimulation of the cavernous nerve, indicating that the cAMP pathway does not play a significant role in penile erection in rats. However, intracavernous administration of methylene blue, a guanylate cyclase inhibitor, significantly reduced the response to electrostimulation (p = 0.001). Direct intracavernous injection of cGMP caused a statistically significant, dose-dependent increase in intravenous pressure that was not significantly inhibited by methylene blue. Sodium nitroprusside, a nitric oxide releaser and therefore a guanylate cyclase activator, caused a dose-dependent increase in intracavernous pressure (p < 0.05) that was inhibited almost completely by methylene blue (p = 0.002), supporting the theory that nitric oxide activates the synthesis of cGMP and that cGMP causes cavernous smooth muscle relaxation. Papaverine elicited an intracavernous pressure increase that was not affected by methylene blue or N-ethylmaleimide, indicating that papaverine acts through an independent pathway.(ABSTRACT TRUNCATED AT 250 WORDS)
Martinez-Piñeiro
L
L
Department of Urology, University of California Medical School, San Francisco.
Trigo-Rocha
F
F
Hsu
G L
GL
von Heyden
B
B
Lue
T F
TF
Tanagho
E A
EA
D000527:Alprostadil / Q000494:pharmacology; D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology; D000242:Cyclic AMP / Q000494:pharmacology / Q000502:physiology; D006152:Cyclic GMP / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D005033:Ethylmaleimide / Q000494:pharmacology; D005971:Glutamates / Q000494:pharmacology; D018698:Glutamic Acid; D008297:Male; D008751:Methylene Blue / Q000494:pharmacology; D009126:Muscle Relaxation / Q000187:drug effects / Q000502:physiology; D016202:N-Methylaspartate / Q000494:pharmacology; D018377:Neurotransmitter Agents / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D010208:Papaverine / Q000494:pharmacology; D010410:Penile Erection / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology
D005971:Glutamates; D018377:Neurotransmitter Agents; D009599:Nitroprusside; D014660:Vasoactive Intestinal Peptide; D018698:Glutamic Acid; D016202:N-Methylaspartate; D010208:Papaverine; D000242:Cyclic AMP; D000527:Alprostadil; D006152:Cyclic GMP; D015740:Calcitonin Gene-Related Peptide; D005033:Ethylmaleimide; D008751:Methylene Blue