Effects of nimodipine and isradipine on endothelin-1-induced contraction of pregnant rat myometrium

The purpose of this study was to investigate the effect of nimodipine and isradipine on endothelin-1-induced contractions of isolated pregnant rat myometrium. Endothelin-1 at 10(-10)-10(-8) M dose-dependently increased the amplitude and frequency of contractions and decreased the duration of contractions. Basal tone of myometrium was increased with the higher endothelin-1 concentrations (10(-9) and 10(-8) M). After pretreatment for 30 min with 10(-6) M nimodipine or 10(-5) M isradipine, amplitude and duration of endothelin-1-induced contractions were significantly decreased, but frequency of myometrial contractions increased markedly. However, neither agent abolished the stimulating effect of higher endothelin-1 concentrations (10(-9) and 10(-8) M) on the basal tone. Our study showed that phasic activity is inhibited by nimodipine and isradipine, whereas tonic activity is not inhibited. The contraction of myometrial strips isolated from the pregnant rat may be modulated by endothelin-1, and this effect is only partly modulated by dihydropyridine-type Ca2+ channels. The remaining resistance to nimodipine-and isradipine-induced inhibition may be explained by pregnancy-associated changes in the other electrophysiological and biochemical factors. (C) 1998 Elsevier Science B.V.