Nitric oxide and cGMP: mediators of pelvic nerve-stimulated erection in dogs.
We sought to determine whether the L-arginine-nitric oxide-guanosine 3',5'-cyclic monophosphate (cGMP) pathway, known to mediate neurostimulation-induced smooth muscle relaxation in penile tissue of rabbits and humans in vitro, is operative also in vivo. Adult male dogs (n = 9) were subjected to direct electrical stimulation of the pelvic nerves to induce penile tumescence. Intracavernous injection of the nitric oxide-releasing substance S-nitroso-N-acetylpenicillamine resulted in similar tumescence. Intracavernous injection of a specific inhibitor of nitric oxide synthesis, NG-nitro-L-arginine, blocked pelvic nerve-stimulated tumescence, and this was partially reversed by intracavernous injection of the nitric oxide precursor L-arginine. Furthermore, neurostimulated tumescence was inhibited by methylene blue, an inhibitor of cytosolic guanylate cyclase and enhanced by M&B 22948, a cGMP phosphodiesterase inhibitor. These in vivo findings support the hypothesis that cavernous smooth muscle relaxation and penile tumescence are mediated by nitric oxide and cGMP.
Trigo-Rocha
F
F
Department of Urology, University of California School of Medicine, San Francisco.
Aronson
W J
WJ
Hohenfellner
M
M
Ignarro
L J
LJ
Rajfer
J
J
Lue
T F
TF
D015106:3',5'-Cyclic-GMP Phosphodiesterases / Q000037:antagonists & inhibitors; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D006152:Cyclic GMP / Q000502:physiology*; D004285:Dogs; D004558:Electric Stimulation; D008297:Male; D008751:Methylene Blue / Q000494:pharmacology; D019331:NG-Nitroarginine Methyl Ester; D009424:Nervous System Physiological Phenomena; D009569:Nitric Oxide / Q000378:metabolism*; D010388:Pelvis / Q000294:innervation*; D010410:Penile Erection / Q000187:drug effects / Q000502:physiology*; D011688:Purinones / Q000494:pharmacology
D011688:Purinones; D009569:Nitric Oxide; D001120:Arginine; D015106:3',5'-Cyclic-GMP Phosphodiesterases; C011145:zaprinast; D006152:Cyclic GMP; D008751:Methylene Blue; D019331:NG-Nitroarginine Methyl Ester