Effects of cholinoceptor blocking drugs, adrenoceptor stimulants, and calcium antagonists on the transmurally stimulated guinea-pig urinary bladder in vitro and in vivo.

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 x 10(-8)-5.9 x 10(-4) M) did not influence the contractions. When used in high concentrations (greater than 5.2 x 10(-5) M), PR 197, another anticholinergic compound, reduced the responses by 25-40%, probably by a non-specific action. Noradrenaline (2.0 x 10(-6)--2.0 x 10(-4) M) and isoprenaline (2.0 x 10(-8)-2.0 x 10(-4) M) had concentration-related inhibitory effects that could be blocked by propranolol (5.2 x 10(-6) M). Adenosine (2.0 x 10(-2) M) inhibited the response by 27 +/- 3% (mean +/- S.E.M., n = 9). Theophylline (2.0 x 10(-5)-6.0 x 10(-4) M) had no consistent effects. The calcium antagonist nifedipone (1.2 x 10(-6)-1.7 x 10(-5) M) reduced the contractions by 25-50%; verapamil (2.2 x 10(-5)-4.4 x 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 microgram/kg) and isoprenaline (20-300 microgram/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 contractions in the guinea-pig urinary bladder.