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.
Department of Urology, University of California School of Medicine, San Francisco.
F
F
Trigo-Rocha
W J
WJ
Aronson
M
M
Hohenfellner
L J
LJ
Ignarro
J
J
Rajfer
T F
TF
Lue
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