Effects of calcium entry blockers on tension development and calcium influx in rat uterus.

Spontaneous and potassium chloride (KCl)-induced tension development of strips of whole uterus from the day-22 pregnant rat was reduced when the tissues were incubated in a calcium ion (Ca2+)-free medium. Strips of whole uterus, in an initially Ca2+-free medium, responded to the cumulative addition of Ca2+ with graded phasic tension development and associated rapid electrical discharges. The spasms were inhibited by gallopamil (100 nM) and diltiazem (1 microM). Strips of whole uterus in a depolarizing (40 mM K+) medium, which was initially Ca2+-free, responded to the cumulative addition of Ca2+ with graded tonic tension development without associated electrical discharges. These spasms were inhibited by calcium entry blockers with a rank order of potency of nifedipine = gallopamil greater than diltiazem greater than cinnarizine. KCl-induced tension development in endometrium-free uterine strips was antagonized by calcium entry blockers with a rank order of potency of nifedipine greater than gallopamil greater than diltiazem greater than cinnarizine. Ca2+ influx into endometrium-free uterine strips was assessed by means of the 'lanthanum method'. KCl induced a concentration-dependent increase in 45Ca2+ influx which was suppressed or abolished by nifedipine (2.5 nM), gallopamil (100 nM), diltiazem (500 nM) or cinnarizine (5 microM). It is concluded that spontaneous and KCl-induced tension development of rat uterus involves Ca2+ influx from the extracellular medium into the myometrial cell. These results support the hypothesis that nifedipine, gallopamil, diltiazem and cinnarizine inhibit Ca2+- and KCl-induced tension development of rat uterus by reduction of Ca2+ influx.