title: Mediation by nitric oxide of neurogenic relaxation of the urinary bladder neck muscle in sheep.
abstract: 1. Mechanical recordings were made in vitro from circularly oriented strips of the bladder neck muscle of sheep. In the absence of drugs, electrical field stimulation at frequencies of 0.2-1 Hz evoked clear-cut relaxations throughout 1 min stimulation periods, while higher stimulus frequencies (2-8 Hz) evoked variable responses consisting of relaxation, contraction or a mixture of both. All of the responses were abolished by tetrodotoxin (10(-6) M). 2. The contractions were reduced by guanethidine (10(-6) M) and atropine (10(-6) M), so that in the presence of these drugs clear-cut relaxations were obtained at 0.2-8 Hz stimulation, indicating that the relaxations were mediated by non-adrenergic, non-cholinergic (NANC) nerves. 3. The NANC relaxations were blocked by L-NG nitro arginine methyl ester (L-NAME), an inhibitor of nitric oxide synthesis. The antagonism by L-NAME was reversed by L-arginine. 4. Another feature of the NANC relaxation was 'rebound contraction' which occurred when the stimulus was switched off. The rebound contraction was also blocked by L-NAME and restored by L-arginine. 5. The relaxations and rebound contractions were unaffected by either alpha,beta-methylene ATP (10(-5) M) or 2-methylthio ATP (10(-5) M). 6. S-Nitroso-L-cysteine, a substance which spontaneously releases NO at physiological pH, mimicked the relaxation and rebound contraction produced by nerve stimulation. 7. It is concluded that nerve-evoked relaxation of the bladder neck is mediated by NO, or a closely related substance such as S-nitroso-L-cysteine.
authors.affiliation: Department of Physiology, School of Biomedical Science, Queen's University of Belfast, Northern Ireland.
authors.forename: K D
authors.initials: KD
authors.lastname: Thornbury
authors.forename: M A
authors.initials: MA
authors.lastname: Hollywood
authors.forename: N G
authors.initials: NG
authors.lastname: McHale
mesh_terms: D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001285:Atropine / Q000494:pharmacology; D003545:Cysteine / Q000031:analogs & derivatives / Q000494:pharmacology; D004558:Electric Stimulation; D005260:Female; D006145:Guanethidine / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects / Q000502:physiology; D009130:Muscle, Smooth / Q000187:drug effects / Q000294:innervation / Q000502:physiology*; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000378:metabolism*; D026403:S-Nitrosothiols; D012756:Sheep; D013873:Thionucleotides / Q000494:pharmacology; D001743:Urinary Bladder / Q000187:drug effects / Q000294:innervation* / Q000502:physiology*
chemical_list: D026403:S-Nitrosothiols; D013873:Thionucleotides; D009569:Nitric Oxide; D001285:Atropine; D000255:Adenosine Triphosphate; C021315:S-nitrosocysteine; D001120:Arginine; D003545:Cysteine; C002630:alpha,beta-methyleneadenosine 5'-triphosphate; D019331:NG-Nitroarginine Methyl Ester; C008501:2-methylthio-ATP; D006145:Guanethidine