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 levcromakalim (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 alpha-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 vasodilating 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 alpha-adrenergic receptors in vascular smooth muscles.
Department of Anesthesiology, Wakayama Medical University, Wakayama, Wakayama, Japan. hkinoshi@pd5.so-net.ne.jp
Hiroyuki
H
Kinoshita
Mayuko
M
Dojo
Katsutoshi
K
Nakahata
Yoshiki
Y
Kimoto
Tetsuya
T
Kakutani
Kazuhiro
K
Mizumoto
Yoshio
Y
Hatano
D000255:Adenosine Triphosphate / Q000502:physiology*; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects* / Q000502:physiology; D019806:Cromakalim / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004329:Droperidol / Q000494:pharmacology*; D004357:Drug Synergism; D066298:In Vitro Techniques; D008297:Male; D015221:Potassium Channels / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology
D015221:Potassium Channels; D019806:Cromakalim; D000255:Adenosine Triphosphate; D004329:Droperidol