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

Abstract

1 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. 2 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 μM). 3 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 > diltiazem > cinnarizine. 4 KCl-induced tension development in endometrium-free uterine strips was antagonized by calcium entry blockers with a rank order of potency of nifedipine > gallopamil > diltiazem > cinnarizine. 5 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 μM). 6 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.