The effects of potassium channel openers on isolated pregnant human myometrium before and after the onset of labor: potential for tocolysis.

Abstract

Our purpose was to investigate the effects and pharmacologic properties of potassium channel openers in isolated pregnant human myometrium. Biopsy specimens of myometrium obtained from 67 women during pregnancy and labor were used for isometric recording under physiologic conditions. Levcromakalim and pinacidil, two prototype potassium channel openers, are potent inhibitors of spontaneous and induced (0.5 nmol/L oxytocin and 10 mumol/L phenylephrine) contractions in isolated human pregnant myometrium, obtained before and after the onset of labor. The sulfonylurea glibenclamide is an apparent competitive antagonist of this inhibition. No antagonism was observed with the sulfonylurea tolbutamide. Both potassium channel openers significantly inhibited contractility evoked by low (10 and 20 mmol/L) but not high (40 and 80 mmol/L) concentrations of extracellular potassium chloride. These findings suggest that the relaxant ability of levcromakalim and pinacidil in human pregnant myometrium is because of potassium channel activation. This introduces a potential new approach for tocolysis.