Nitric oxide and cyclic GMP formation upon electrical field stimulation cause relaxation of corpus cavernosum smooth muscle.
In the presence of functional adrenergic and cholinergic blockade, electrical field stimulation relaxes corpus cavernosum smooth muscle by unknown mechanisms. We report here that electrical field stimulation of isolated strips of rabbit corpus cavernosum promotes the endogenous formation and release of nitric oxide (NO), nitrite, and cyclic GMP. Corporal smooth muscle relaxation in response to electrical field stimulation, in the presence of guanethidine and atropine, was abolished by tetrodotoxin and potassium-induced depolarization, and was markedly inhibited by NG-nitro-L-arginine, NG-amino-L-arginine, oxyhemoglobin, and methylene blue, but was unaffected by indomethacin. The inhibitory effects of NG-substituted analogs of L-arginine were nearly completely reversed by addition of excess L-arginine but not D-arginine. Corporal smooth muscle relaxation elicited by electrical field stimulation was accompanied by rapid and marked increases in tissue levels of nitrite and cyclic GMP, and all responses were nearly abolished by NG-nitro-L-arginine. These observations indicate that penile erection may be mediated by NO generated in response to nonadrenergic-noncholinergic neurotransmission.
Ignarro
L J
LJ
Department of Pharmacology, University of California, Los Angeles 90024.
Bush
P A
PA
Buga
G M
GM
Wood
K S
KS
Fukuto
J M
JM
Rajfer
J
J
D000818:Animals; D001120:Arginine / Q000494:pharmacology; D001285:Atropine / Q000494:pharmacology; D006152:Cyclic GMP / Q000096:biosynthesis*; D004558:Electric Stimulation; D006145:Guanethidine / Q000494:pharmacology; D008297:Male; D008564:Membrane Potentials; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology*; D009569:Nitric Oxide / Q000378:metabolism*; D010413:Penis / Q000187:drug effects*; D011188:Potassium / Q000494:pharmacology; D011817:Rabbits; D009435:Synaptic Transmission; D013779:Tetrodotoxin / Q000494:pharmacology
D009569:Nitric Oxide; D013779:Tetrodotoxin; D001285:Atropine; D001120:Arginine; D006152:Cyclic GMP; D011188:Potassium; D006145:Guanethidine