THE EFFECTS OF POTASSIUM CHANNEL OPENERS ON ISOLATED PREGNANT HUMAN MYOMETRIUM BEFORE AND AFTER THE ONSET OF LABOR - POTENTIAL FOR TOCOLYSIS

OBJECTIVE: Our purpose was to investigate the effects and pharmacologi c properties of potassium channel openers in isolated pregnant human m yometrium. STUDY DESIGN: Biopsy specimens of myometrium obtained from 67 women during pregnancy and labor were used for isometric recording under physiologic conditions. RESULTS: Levcromakalim and pinacidil, tw o prototype potassium channel openers, are potent inhibitors of sponta neous and induced (0.5 nmol/L oxytocin and 10 mumol/L phenylephrine) c ontractions in isolated human pregnant myometrium, obtained before and after the onset of labor. The sulfonylurea glibenclamide is an appare nt competitive antagonist of this inhibition. No antagonism was observ ed with the sulfonylurea tolbutamide. Both potassium channel openers s ignificantly inhibited contractility evoked by low (10 and 20 mmol/L) but not high (40 and 80 mmol/L) concentrations of extracellular potass ium chloride. CONCLUSION: These findings sugggest that the relaxant ab ility of levcromakalim and pinacidil in human pregnant myometrium is b ecause of potassium channel activation. This introduces a potential ne w approach for tocolysis.