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-mu-M). 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-N(G)-nitro arginine (L-NOARG; 0.3-100-mu-M) but not by D-N(G)-nitro arginine. The inhibitory effect of L-NOARG on transmission was antagonized by L-arginine (100-mu-M), a NO precursor, but not by D-arginine. 4 Incubation with methylene blue (10-50-mu-M), 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.