Electrically-induced, nerve-mediated relaxation of rabbit urethra involves nitric oxide

Abstract

Isolated smooth muscle preparations from the rabbit urethra precontracted with noradrenaline (10(-5) M), endothelin (10(-7) M), or arginine vasopressin (10(-7) M) responded to electrical field stimulation by frequency-dependent non-adrenergic, non-cholinergic relaxations, which could be blocked by tetrodotoxin (10(-6) M). Relaxation was more pronounced in preparations precontracted by endothelin than by noradrenaline or arginine vasopressin. The electrically induced relaxations were reduced in a concentration-dependent manner by pretreatment for 30 minutes with NG-nitro-L-arginine (10(-6) to 10(-4) M) and NG-monomethyl-L-arginine (10(-5) to 10(-4) M). At the highest concentration of NG-nitro-L-arginine used (10(-4) M), relaxation was abolished and/or changed into a contraction. The effect of NG-nitro-L-arginine was reversible. NG-nitro-D-arginine had no effect. Pretreatment for 30 minutes with L-arginine (10(-3) M) slightly, but significantly, enhanced the maximum relaxation to field stimulation in noradrenaline-precontracted preparations. L-arginine pretreatment also prevented the effects of low, but not high, concentrations of NG-nitro-L-arginine. In contrast, D-arginine had no effect. Electrically induced relaxations were not significantly affected by methylene blue (10(-5) M) or superoxide dismutase (20 U/ml). Addition of nitric oxide (present in acidified solution of NaNO2) caused transient and concentration-dependent relaxations in preparations precontracted by noradrenaline. At the maximum concentration used (10(-3) M), the relaxant response averaged 67% of the tension induced by noradrenaline. Nitric-oxide-induced relaxations were not affected by NG-nitro-L-arginine or L-arginine, but were significantly inhibited by methylene blue. In preliminary experiments, effects similar to those found in rabbit urethra were also observed in isolated urethral preparations obtained from three patients. It is suggested that in the urethra, nitric oxide is involved in the mediation of relaxation evoked by electrical stimulation of nerves.