Relaxation of sheep urethral muscle induced by electrical stimulation of nerves: involvement of nitric oxide

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Abstract
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 F2α. 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 noradrenaline, 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 NG‐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, relaxation was changed into a contraction. NO (present in acidified solution of NaNO2) still produced relaxation. NG‐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.