The effect of inhibitors of nitric oxide biosynthesis and cyclic GMP formation on nerve-evoked relaxation of human cavernosal smooth muscle.
1. The inhibitory transmission in isolated preparations of cavernosal smooth muscle from human penis has been studied. 2. Electrical field stimulation (EFS; 2-64 pulses/train, 0.8 ms pulse duration, 10 Hz) evoked relaxation of preparations treated with guanethidine (50 microM). The EFS-evoked relaxations were atropine-resistant and tetrodotoxin-sensitive indicating their origin to be non-adrenergic, non-cholinergic (NANC) nerve stimulation. 3. EFS-evoked relaxation was attenuated dose-dependently by the nitric oxide (NO)-synthase inhibitor, L-NG-nitro arginine (L-NOARG; 0.3-100 microM) but not by D-NG-nitro arginine. The inhibitory effect of L-NOARG on transmission was antagonized by L-arginine (100 microM), a NO precursor, but not by D-arginine. 4. Incubation with methylene blue (10-50 microM), a known inhibitor of guanylate cyclase activation by NO, caused a concentration-related inhibition of EFS-evoked relaxation. 5. It is concluded that NANC nerve-evoked relaxation of human cavernosal smooth muscle is mediated by NO or a NO-like substance.
Pickard
R S
RS
Department of Pharmacological Sciences Medical School, Newcastle upon Tyne.
Powell
P H
PH
Zar
M A
MA
D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001341:Autonomic Nervous System / Q000187:drug effects; D006152:Cyclic GMP / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D004558:Electric Stimulation; D006145:Guanethidine / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008751:Methylene Blue / Q000494:pharmacology; D009126:Muscle Relaxation / Q000502:physiology; D009130:Muscle, Smooth / Q000294:innervation / Q000502:physiology*; D009569:Nitric Oxide / Q000037:antagonists & inhibitors* / Q000378:metabolism; D019335:Nitroarginine; D010413:Penis / Q000187:drug effects / Q000294:innervation; D009435:Synaptic Transmission / Q000187:drug effects
D019335:Nitroarginine; D009569:Nitric Oxide; D001120:Arginine; D006152:Cyclic GMP; D008751:Methylene Blue; D006145:Guanethidine