RESPONSE OF GUINEA-PIG SMOOTH AND STRIATED URETHRAL SPHINCTER TO CROMAKALIM, PRAZOSIN, NIFEDIPINE, NITROPRUSSIDE, AND ELECTRICAL-STIMULATION

Prazosin (an alpha-l-adrenegic blocker) and cromakalim (potassium chan nel opener), given alone, induced significant fatigue of the urethral sphincter at a concentration of 10(-4) M; both drugs combined achieved a significant sphincteric fatigue at a concentration of 10(-5) M each . To 10(-4) M hexamethonium (ganglionic smooth muscle blocker) and 10( -4) M decamethonium (nicotinic blocker of striated muscle) the striate d urethral sphincter responded like striated muscle with no detectable function of its smooth muscle component. Therefore, the striated comp onent seems to play a dominant role in sphincteric function. With calc ium depletion or in the presence of a calcium channel blocker (10(-4) M nifedipine) the urethral sphincter showed a relative enhancement of response to electrical field stimulation when compared with smooth and skeletal muscle, whose responses were both significantly reduced. Thi s phenomenon could not be explained with calcium-dependent, inhibitory , nitric oxide-releasing nerves, as the NO-synthase blocker N-nitro-L- arginine (10(-5) M to 5 x 10(-5) M) failed to induce the enhancement o f sphincter contraction during electrostimulation found with calcium d epletion. Still, NO-releasing nerves might play a role in sphincteric relaxation because sodium nitroprusside (10(-5) M) induced a significa nt relaxation of the urethral sphincter precontracted with 80 mM potas sium. The potential to weaken sphincteric closure with drugs, exemplif ied by the results obtained in response to prazosin and cromakalim, wo uld represent a therapeutic advance in the patient with neurogenic bla dder dysfunction. (C) 1995 Wiley-Liss. Inc.