Augmented activity of adenosine triphosphate-sensitive K+ channels induced by droperidol in the rat aorta

Droperidol produces the inhibition of K+ channels in cardiac myocytes. However, the effects of droperidol on K+ channels have not been studied in blood vessels. Therefore, we designed the present study to determine whether droperidol modulates the activity of adenosine triphosphate (ATP)-sensitive K+ channels in vascular smooth muscle cells. Rat aortic rings without endothelium were suspended or used for isometric force and membrane potential recordings, respectively. Vasorelaxation and hyperpolarization induced by levcro-makalim (10(-8) to 10(-5) M or 10(-5) M, respectively) were completely abolished by the ATP-sensitive K+ channel antagonist glibenclamide (10(-5) M). Droperidol (10(-7) M) and an a-adrenergic receptor antagonist phentolamine (3 X 10(-9) M) caused a similar vasodilator effect (approximately 20% of vasorelaxation compared with maximal vasorelaxation induced by papaverine [3 X 10(-4) M]), whereas glibenclamide did not alter vasorelaxation induced by droperidol. Droperidol (3 X 10(-8) M to 10(-7) M) augmented vasorelaxation and hyperpolarization produced by levcromakalim, whereas phentolamine (3 X 10(-9) M) did not alter this vasorelaxation. Glibenclamide (10(-5) M) abolished the vasoctilating and hyperpolarizing effects of levcromakalim in the aorta treated with droperidol (10(-7) M). These results suggest that droperidol augments vasodilator activity via ATP-sensitive K+ channels. However, it is unlikely that this augmentation is mediated by the inhibition of a-adrenergic receptors in vascular smooth muscles.