RELAXATION OF SHEEP URETHRAL MUSCLE INDUCED BY ELECTRICAL-STIMULATION OF NERVES - INVOLVEMENT OF NITRIC-OXIDE

Isolated smooth muscle preparations from the sheep urethra responded to electrical field stimulation with contraction when basal tension was low (5-6 mN), but with relaxation when the preparations were contracted with noradrenaline (NA), clonidine, or prostaglandin F2-alpha. No relaxant response could be elicited in high K+ (124 mM) contracted preparations. Electrically induced relaxations had a threshold of less than 1 Hz and a maximum at 8 Hz. Both contractant and relaxant responses were abolished by tetrodotoxin, indicating that they were caused by transmitters released from nerves. The amplitude of the relaxant responses showed a highly significant correlation to the tension induced by noradrenaline. A coefficient (R/T) was calculated relating relaxation to noradrenaline-induced tension. In this way it is possible to separate the effect of drugs on muscle tension (non-specific effect) from their action on the electrically induced relaxation (specific effect). Chemical sympathectomy with 6-OHDA did not significantly modify the relaxant response to 6 Hz in noradrenaline contracted strips,as evaluated by the R/T coefficient. The electrically induced relaxation was not affected by hexamethonium, propranolol, phentolamine, muscarinic receptor blockade, cocaine, indomethacin, or methysergide. Both nifedipine and Bay K 8644 inhibited significantly the response induced by electrical stimulation, decreasing its maximum. Nifedipine, but not Bay K 8644, significantly reduced the level of tension induced by noradenaline, and its effect, evaluated by the R/T coefficient, was an increase in the electrically induced relaxation, whereas Bay K 8644 had a significant inhibitory effect. Pre-treatment with N(G)-nitro-L-arginine (L-NOARG) for 30 minutes did not significantly change resting tension,but concentration-dependently reduced the relaxant responses, and at the highest L-NOARG concentration used, relaation was changed into a contraction. NO (present in acidified solution of NaNO2) still produced relaxation. N(G)-nitro-D-arginine (D-NOARG) had no effects. It is suggested that in contracted sheep urethral muscle,the relaxation produced by electrical stimulation of nerves is mediated by NO.