Interactive effect of sevoflurane with isradipine or indomethacin on spontaneous contractile activity of isolated pregnant rat myometrium

Abstract

Volatile anesthetics, calcium antagonists and non-steroidal anti-inflammatory drugs inhibit contractile activity of myometrial smooth muscle. The aim of this study was to investigate the interactive effect of sevoflurane with isradipine or indomethacin on spontaneous contractile activity of myometrial strips isolated from pregnant rats. The myometrial strips were excised from rats (250-300 g) at 19-21 days of gestation and mounted in tissue baths for recording of isometric tension. Sevoflurane (0.5 to 3 MAC) inhibited the amplitude and frequency of spontaneous myometrial contractions in a concentration-dependent manner (P<0.05). Sevoflurane responses were repeated in the presence of isradipine (a dihydropyridine-type calcium channel blocker) and indomethacin (a non-selective cyclooxygenase (COX) inhibitor). Pretreatment with isradipine (10(-6) M) or indomethacin (10(-7) M), concentrations that themselves had no effect on spontaneous contractility, significantly increased the inhibitor responses to sevoflurane on amplitude and frequency of myometrial contractions, beginning at 1 MAC (P<0.05). Blockade of calcium channels in myometrial smooth muscle may increase the inhibitor effect of sevoflurane. Further work is needed to determine the cellular mechanism(s) of this interaction.