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The potencies of four calcium antagonists (nifedipine, gallopamil, verapamil and diltiazem) at inhibiting uterine contractions in vivo have been assessed in the conscious ovariectomized, post-partum rat. Their selectivities for this action, relative to their effects on blood pressure and heart rate, have been compared with salbutamol. All compounds produced a dose-dependent inhibition of intra-uterine pressure cycles. The rank order of potency was salbutamol greater than nifedipine greater than diltiazem = gallopamil greater than verapamil. All compounds produced a dose-dependent fall of mean blood pressure. The rank order of potency was salbutamol greater than nifedipine greater than gallopamil greater than verapamil greater than diltiazem. Salbutamol and nifedipine produced a tachycardia, which was very marked with salbutamol. Gallopamil, verapamil and diltiazem induced a moderate tachycardia at low doses but temporary cessation of heart beat occurred at high doses. Nifedipine and diltiazem, like salbutamol, exhibited some selectivity for inhibition of uterine contractions relative to their cardiovascular actions. Gallopamil and verapamil showed no selectivity for the uterus.

The sensitivity of the uterus to the inhibition of contractions by salbutamol, diltiazem or nifedipine was assessed in the ovariectomized, post-partum rat by dose-response curves following bolus intravenous (i.v.) administration. These tests were performed before (day 1), immediately after a 20 h i.v. infusion of salbutamol, diltiazem, nifedipine or appropriate control infusate (day 2) and after a further 20 h infusion of saline (day 3). In a further group of animals sensitivity to nifedipine was assessed before and after a 20 h infusion of salbutamol. Uterine contractions were monitored throughout infusions. Infusion of salbutamol (2 micrograms kg-1 min-1) produced an initial marked inhibition of uterine contractions, an effect which was not maintained despite continued infusion. Contractions reappeared after 2 h of infusion and reached pre-infusion levels by 5 h. The dose-response curve to salbutamol on day 2 was shifted more than 100 fold to the right compared with that on day 1. Sensitivity of the uterus on day 3 did not differ from that on day 1. Nifedipine (25 micrograms kg-1 min-1) produced sustained inhibition of uterine contractions throughout the 20 h of infusion. Sensitivity of the uterus to nifedipine could not, therefore, be tested on day 2; sensitivity on day 3 did not differ from that on day 1. In addition, there was no change in sensitivity of the uterus to nifedipine after a 20 h infusion of salbutamol. 4 Diltiazem (200 Ig kg-' min-') produced a marked initial inhibition of uterine contractions, with a partial return of contractions during continued infusion in 7 out of 12 animals so that mean integral values reached 40% of those pre-infusion. The dose-response curve to diltiazem on day 2 showed a 25 fold shift to the right compared with that on day 1 in 4 out of 12 animals where the test could be performed. Sensitivity of the uterus on day 3 did not differ from that on day 1. 5 These findings suggest that marked but reversible tolerance to the inhibitory actions of salbutamol on uterine contractions occurs during long-term infusion. There was no evidence of tolerance to the uterine actions of nifedipine, but there was evidence of tolerance to diltiazem in some animals.