title: Response of guinea pig smooth and striated urethral sphincter to cromakalim, prazosin, nifedipine, nitroprusside, and electrical stimulation.
abstract: Prazosin (an alpha-1-adrenergic blocker) and cromakalim (potassium channel 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 striated urethral sphincter responded like striated muscle with no detectable function of its smooth muscle component. Therefore, the striated component seems to play a dominant role in sphincteric function. With calcium 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. This 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 of sphincter contraction during electrostimulation found with calcium depletion. Still, NO-releasing nerves might play a role in sphincteric relaxation because sodium nitroprusside (10(-5) M) induced a significant relaxation of the urethral sphincter precontracted with 80 mM potassium. The potential to weaken sphincteric closure with drugs, exemplified by the results obtained in response to prazosin and cromakalim, would represent a therapeutic advance in the patient with neurogenic bladder dysfunction.
authors.affiliation: Department of Urology, University of California School of Medicine, San Francisco, USA.
authors.forename: B
authors.initials: B
authors.lastname: von Heyden
authors.forename: R K
authors.initials: RK
authors.lastname: Riemer
authors.forename: L
authors.initials: L
authors.lastname: Nunes
authors.forename: G B
authors.initials: GB
authors.lastname: Brock
authors.forename: T F
authors.initials: TF
authors.lastname: Lue
authors.forename: E A
authors.initials: EA
authors.lastname: Tanagho
mesh_terms: D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001578:Benzopyrans / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology; D002148:Calmodulin-Binding Proteins / Q000494:pharmacology; D019806:Cromakalim; D003650:Decamethonium Compounds / Q000494:pharmacology; D004558:Electric Stimulation; D006168:Guinea Pigs; D018738:Hexamethonium / Q000494:pharmacology; D006651:Histocytochemistry; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D009126:Muscle Relaxation / Q000187:drug effects; D018482:Muscle, Skeletal / Q000187:drug effects / Q000473:pathology; D009130:Muscle, Smooth / Q000187:drug effects / Q000473:pathology; D009543:Nifedipine / Q000494:pharmacology*; D019001:Nitric Oxide Synthase; D009599:Nitroprusside / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D011758:Pyrroles / Q000494:pharmacology; D014521:Urethra / Q000033:anatomy & histology / Q000187:drug effects* / Q000473:pathology
chemical_list: D000959:Antihypertensive Agents; D001578:Benzopyrans; D002148:Calmodulin-Binding Proteins; D003650:Decamethonium Compounds; D011758:Pyrroles; D019806:Cromakalim; D009599:Nitroprusside; D018738:Hexamethonium; C033019:decamethonium; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D009543:Nifedipine; D002118:Calcium; D011224:Prazosin