CYCLIC GUANOSINE-MONOPHOSPHATE MEDIATES PENILE ERECTION IN THE RAT

Recent in vivo and in vitro studies suggest that nitric oxide or a nit ric-oxide-like substance mediates nonadrenergic, noncholinergic relaxa tion of trabecular smooth muscle through activation of the cyclic guan osine monophosphate (cGMP) pathway. In 60 Sprague-Dawley rats, we inve stigated the effect of intracavernous administration of different drug s known to act at different levels of the cyclic adenosine monophospha te (cAMP) and cGMP pathways. Neither cAMP nor drugs that stimulate ade nylate cyclase activity (vasoactive intestinal peptide, prostaglandin E(I), calcitonin gene-related peptide) provoked any change in the basa l intracavernous pressure. N-ethylmaleimide, an inhibitor of the enzym e adenylate cyclase, did not modify the response to electrostimulation of the cavernous nerve, indicating that the cAMP pathway does not pla y a significant role in penile erection in rats. However, intracaverno us administration of methylene blue, a guanylate cyclase inhibitor, si gnificantly reduced the response to electrostimulation (p=0.001). Dire ct intracavernous injection of cGMP caused a statistically significant , dose-dependent increase in intravernous pressure that was not signif icantly inhibited by methylene blue. Sodium nitroprusside, a nitric ox ide releaser and therefore a guanylate cyclase activator, caused a dos e-dependent increase in intracavernous pressure (p<0.05) that was inhi bited almost completely by methylene blue (p=0.002), supporting the th eory that nitric oxide activates the synthesis of cGMP and that cGMP c auses cavernous smooth muscle relaxation. Papaverine elicited an intra cavernous pressure increase that was not affected by methylene blue or N-ethylmaleimide, indicating that papaverine acts through an independ ent pathway. N-methyl-D-aspartate and L-glutamic acid, excitatory amin o acids that act in the central nervous system by stimulating nitric o xide synthase, had no effect on the intracavernous pressure. 5-Hydroxy tryptamine, which is believed to cause presynaptic inhibition of relea se of excitatory amino acids, caused a potent inhibition of the cavern ous response to electrostimulation (p<0.001). It appears that cavernou s smooth muscle relaxation is mediated by the release of a nitric-oxid e-like substance with subsequent activation of guanylate cyclase. The cAMP system seems to play no important role in this mechanism in the r at.