Nitrendipine prolongs rat parturition: no changes occur in progesterone withdrawal

The mechanism of tocolytic action of the calcium channel-blocking agent nitrendipine [3-ethyl-5-methyl-1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl) 3,5-pyridinedicarboxylate; BAYER E 5009] had been examined. Pregnant rats (duration of pregnancy, 22 days) were treated with nitrendipine (12.5 mg/kg, sc) on days 18-21 of gestation (group I) or on days 20-21 of gestation (group II) and with vehicle only (control group). Serum levels of progesterone from the three experimental groups were determined on days 20 and 22, and the course of labor was monitored on days 22-23 in the individually caged dams. The duration of labor, delivery times, and other labor parameters were significantly delayed in the treated groups vs. the control group, while there was no difference in serum progesterone levels among the three experimental groups on day 20 or 22 of gestation 136.0 +/- 5.6 (mean +/- SEM; (n = 6) and 43.8 +/- 7.2 (n = 17) ng progesterone/ml serum, respectively. We can conclude that progesterone withdrawal, the primary event in the initiation of rat labor, is not altered by nitrendipine treatment. The delay of labor is apparently related to a decrease in the contractile state of myometrium due to the inhibition of calcium influx by nitrendipine.