Effects of Cholinoceptor Blocking Drugs, Adrenoceptor Stimulants, and Calcium Antagonists on the Transmurally Stimulated Guinea-pig Urinary Bladder in Vitro and in Vivo

Abstract

The effects of different drugs on the response to transmural electrical stimulation of the guinea-pig urinary bladder were studied in vitro and in vivo. In vitro atropine (3.0 .times. 10-8 to 5.9 .times. 10-4 M) did not influence the contractions. When used in high concentrations (> 5.2 .times. 10-5 M), PR 197 [heptyldimethyl-(1-methyl-3,3-diphenyl-propyl)-ammonium chloride], another anticholinergic compound, reduced the responses by 25-40%, probably by a non-specific action. Noradrenaline [norepinephrine] (2.0 .times. 10-6 to 2.0 .times. 10-4 M) and isoprenaline (2.0 .times. 1008 to 2.0 .times. 10-4 M) had concentration-related inhibitory effects that could be blocked by propranolol (5.2 .times. 10-6 M). Adenosine (2.0 .times. 10-2 M) inhibited the response by 27 .+-. 3% (mean .+-. S.E.M. [standar error of the mean] n = 9). Theophylline (2.0 .times. 10-5 to 6.0 .times. 10-4 M) had no consistent effects. The Ca antagonist nifedipine (1.2 .times. 10-6 to 1.7 .times. 10-5 M) reduced the contractions by 25-50%; verapamil (2.2 .times. 10-5 to 4.4 .times. 10-4 M) was little effective. In vivo, atropine (10 mg/kg) reduced the contractions by 55 .+-. 5% (n = 10), whereas PR 197 (5 mg/kg) almost completely suppressed the responses. Noradrenaline (20-100 .mu.g/kg) and isoprenaline (20-300 .mu.g/kg) also caused a marked inhibition that could be blocked by propranolol (0.25-2.0 mg/kg). Theophylline (5 and 10 mg/kg) had a weak (10-20%) inhibitory effect. Adenosine (3.0 mg/kg) reduced the contractions by 47 .+-. 4% (n = 14); in guinea-pigs pretreated with atropine (10 mg/kg), adenosine produced a further 10 to 20% decrease of the responses. Verapamil (0.5-2.0 mg/kg) had no consistent effect, whereas nifedipine (0.1-0.2 mg/kg) caused an inhibition of 20-50%. The results suggest that .beta.-adrenoceptor stimulants, and drugs with a combined anticholinergic and non-specific action, can effectively suppress the electrically evoked contraction in the guinea-pig urinary bladder.