Kinoshita Hiroyuki, Dojo Mayuko, Nakahata Katsutoshi, Kimoto Yoshiki, Kakutani Tetsuya, Mizumoto Kazuhiro, Hatano Yoshio
Department of Anesthesiology, Wakayama Medical University, Wakayama, Wakayama, Japan.
Anesth Analg. 2006 Mar;102(3):786-91. doi: 10.1213/01.ane.0000195441.14929.6d.
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.
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。
