氟哌利多诱导大鼠主动脉中三磷酸腺苷敏感性钾通道活性增强。

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

作者信息

Kinoshita Hiroyuki, Dojo Mayuko, Nakahata Katsutoshi, Kimoto Yoshiki, Kakutani Tetsuya, Mizumoto Kazuhiro, Hatano Yoshio

机构信息

Department of Anesthesiology, Wakayama Medical University, Wakayama, Wakayama, Japan.

出版信息

Anesth Analg. 2006 Mar;102(3):786-91. doi: 10.1213/01.ane.0000195441.14929.6d.

DOI:10.1213/01.ane.0000195441.14929.6d

PMID:16492829

Abstract

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.

摘要

氟哌利多可抑制心肌细胞中的钾通道。然而，氟哌利多对血管中钾通道的影响尚未得到研究。因此，我们设计了本研究，以确定氟哌利多是否能调节血管平滑肌细胞中三磷酸腺苷（ATP）敏感性钾通道的活性。分别将无内皮的大鼠主动脉环悬挂起来或用于等长力和膜电位记录。ATP敏感性钾通道拮抗剂格列本脲（10⁻⁵ M）可完全消除由左卡尼汀（分别为10⁻⁸至10⁻⁵ M或10⁻⁵ M）诱导的血管舒张和超极化。氟哌利多（10⁻⁷ M）和α-肾上腺素能受体拮抗剂酚妥拉明（3×10⁻⁹ M）产生了相似的血管舒张作用（与罂粟碱[3×10⁻⁴ M]诱导的最大血管舒张相比，约为血管舒张的20%），而格列本脲并未改变氟哌利多诱导的血管舒张。氟哌利多（3×10⁻⁸ M至10⁻⁷ M）增强了左卡尼汀产生的血管舒张和超极化作用，而酚妥拉明（3×10⁻⁹ M）并未改变这种血管舒张。格列本脲（10⁻⁵ M）消除了在经氟哌利多（10⁻⁷ M）处理的主动脉中左卡尼汀的血管舒张和超极化作用。这些结果表明，氟哌利多通过ATP敏感性钾通道增强血管舒张活性。然而，这种增强不太可能是由血管平滑肌中α-肾上腺素能受体的抑制介导的。