Characterization of inhibitory neurotransmission in the isolated corpus cavernosum from rabbit and man.
1. NG-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, 5 s 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 NG-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.(ABSTRACT TRUNCATED AT 400 WORDS)
Holmquist
F
F
Department of Clinical Pharmacology, Lund University Hospital, Sweden.
Hedlund
H
H
Andersson
K E
KE
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D004558:Electric Stimulation; D006801:Humans; D008297:Male; D008981:Molsidomine / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009569:Nitric Oxide / Q000378:metabolism; D019335:Nitroarginine; D010413:Penis / Q000187:drug effects / Q000378:metabolism; D011817:Rabbits; D009435:Synaptic Transmission / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology
D014665:Vasodilator Agents; D019335:Nitroarginine; D009569:Nitric Oxide; C002385:linsidomine; D001120:Arginine; D008981:Molsidomine