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 μm). 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 μm) but not by d‐NG‐nitro arginine. The inhibitory effect of l‐NOARG on transmission was antagonized by l‐arginine (100 μm), a NO precursor, but not by d‐arginine. 4 Incubation with methylene blue (10–50 μm), 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.