Capsaicin-induced nitric-oxide-dependent relaxation in isolated dog urethra

Capsaicin (5 x 10[-8] to 5 x 10[-5] M) produced a non-adrenergic and non-cholinergic phasic relaxation in a concentration-dependent manner in isolated dog urethral preparations precontracted by noradrenaline. The mode of action of capsaicin was investigated with special reference to the possible involvement of endogenous nitric oxide (NO). A marked tachyphylaxis was observed in the responses to capsaicin. Pretreatment with NG-nitro-L-arginine-methyl-ester (L-NAME) prevented or markedly reduced the inhibitory effect of L-NAME. Methylene blue inhibited the capsaicin-induced relaxation. In preparations stored at 4 degrees C for 72 h, the reduction in the capsaicin-induced relaxation was significantly greater than that in the relaxation induced by either electrical field stimulation or by sodium nitroprusside. We conclude that capsaicin produces an endogenous-NO-dependent relaxation in the isolated dog urethra via mechanisms that deteriorate during cold storage of the preparations.