CHARACTERIZATION OF INHIBITORY NEUROTRANSMISSION IN THE ISOLATED CORPUS CAVERNOSUM FROM RABBIT AND MAN

1. N(G)-nitro-L-arginine (L-NOARG, 10(-4) M), an inhibitor of nitric oxide (NO) synthesis, had no contractile effect on isolated preparations of rabbit and human corpus cavernosum at baseline tension, but increased tension in preparations contracted by noradrenaline (rabbit 10(-5) M, man 3 x 10(-7)-3 x 10(-6) M) or K+ (rabbit 60 mM). 2. Electrical field stimulation (supramaximal voltage, 0.8 ms pulses, 5s train duration, 0.5-35 Hz) of rabbit and human corpus cavernosum preparations contracted by noradrenaline (rabbit 10(-5) M, man 3 x 10(-6) M) or endothelin-1 (rabbit 10(-8) M) produced relaxations that were sensitive to tetrodotoxin (10(-6) M), and dependent on the frequency and number of pulses delivered. L-NOARG (10(-6)-10(-4) M), but not N(G)-nitro-D-arginine (D-NOARG, 10(-6)-10(-4) M), inhibited electrically induced relaxations in a concentration-dependent manner, and at 10(-4) M the relaxations were virtually abolished. L-Arginine (10(-3) M), but not D-arginine (10(-3) M), partly reversed the inhibitory effect of L-NOARG (10(-4) M). In rabbit corpus cavernosum preparations, as with Methylene Blue (3 x 10(-5) M), an inhibitor of the soluble guanylate cyclase, and haemoglobin (10(-5) M), sequestering NO in the extracellular space, significantly reduced electrically evoked relaxations. Scopolamine (10(-6) M) had little or no effect on relaxations induced by electrical field stimulation. 3. Preparations of rabbit and human corpus cavernosum contracted by noradrenaline (rabbit 10(-5) M, man 3 x 10(-6) M) were relaxed by carbachol (10(-9)-10(-4) M) in a concentration-dependent manner. Scopolamine (10(-6) M) and L-NOARG (10(-4) M) abolished, and Methylene Blue (3 x 10(-5) M) and haemoglobin (10(-5) M) greatly reduced, the carbachol-induced relaxation, while D-NOARG (10(-4) M) had no significant effect. 4. In rabbit corpus cavernosum preparations contracted by noradrenaline (10(-5) M), L-NOARG (10(-4) M) had no significant effect on relaxations induced by vasoactive intestinal polypeptide (10(-6) M). 5. SIN-1 (3-morpholino-sydnonimin hydrochloride, 10(-8)-3 x 10(-4) M), which spontaneously liberates NO, relaxed preparations of rabbit and human corpus cavernosum contracted by noradrenaline (rabbit 10(-5) M, man 3 x 10(-6) M) or endothelin-1 (rabbit 10(-8) M, man 3 x 10(-9) M) in a concentration-dependent way. The relaxing effect of SIN-1 was enhanced by L-NOARG (10(-4) M) and Methylene Blue (rabbit 3 x 10(-5) M, man 10(-5) M). 6. The results suggest that the inhibitory neurotransmission in corpus cavernosum is mediated mainly by NO, or a NO-containing compound. NO, derived from L-arginine, seems to act, at least partly, through stimulation of soluble guanylate cyclase. Whether NO is released indirectly via the action of some as yet unidentified non-adrenergic, non-cholinergic transmitter, or directly from a neuronal source, remains to be established.