Deactivation of the uterus during normal and premature labor by the calcium antagonist nicardipine

Abstract

Nicardipine, a calcium antagonist, suspended the spontaneous activity of the excised rabbit uterus at a concentration of 1 μg/ml and abolished the electrical excitability at a concentration of 10 μg/ml. In situ, single doses of 100 and 500 μg reversibly suspended the spontaneous activity of the postpartum rat uterus (n = 22) for 34 ± 6 minutes and 94 ± 9 minutes, respectively. Furthermore, the intrauterine administration of prostaglandin F2α or oxytocin failed to elevate intrauterine pressure in the postpartum rats (n = 18) injected with an average dose of 207 ± 28 μg of nicardipine. The administration of nicardipine to the rats (n = 19) immediately after the spontaneous delivery of the first fetus arrested labor, and the delivery of the subsequent fetuses was markedly delayed as compared to the control rats (n = 20). Similarly, when premature labor was induced by ovariectomy (OVX) on day 16, OVX control rats (n = 6) receiving 5 μg/day of estradiol delivered 82% of the fetuses within 48 hours of OVX, whereas the rats treated with nicardipine (n = 7) delivered only 4% of the fetuses. All fetuses were delivered alive and were normal. Since the estradiol, progesterone, and prostaglandin profiles in the heart plasma, uterine vein plasma, and uterine tissue of the control and experimental rats were similar, the prevention of premature labor resulted from the antagonistic action of nicardipine to calcium.