Effects of a Novel Benzodiazepine Derivative, JM-1232(-), on Human Gastroepiploic Artery In Vitro
Effects of a Novel Benzodiazepine Derivative, JM-1232(-), on Human Gastroepiploic Artery In Vitro
复制标题
DOI：
10.1053/j.jvca.2010.03.013
复制
发表时间：
2011-02-01
影响因子：
2.8
通讯作者：
Kanmura, Yuichi
中科院分区：
文献类型：
--
作者：
Moriyama, Takahiro;Tsuneyoshi, Isao;Kanmura, Yuichi
目的：观察JM-1232（-）对去甲肾上腺素(10(-6)mol/L)-和高K+ (40 mmol/L)诱导的离体人胃网膜动脉（GEA）收缩的影响，并与咪达唑仑和异丙酚的作用进行比较。此外，研究苯二氮卓类受体拮抗剂氟马西尼或mu-阿片受体拮抗剂纳洛酮是否影响JM-1232（-）的血管作用。设计：体外实验研究。环境：大学实验室。参与者：GEA片段来自69例接受冠状动脉搭桥手术的患者。测量和主要结果：JM-1232（-）在环中产生剂量依赖的松弛效应。虽然JM-1232（-）在高浓度(10（-5)-10(-4)mol/L）下的松弛作用大于咪达唑仑和异丙酚，但在临床浓度(3 × 10(-6) mol/L、3 × 10（-6) mol/L咪达唑仑和1 × 10(-5) mol/L异丙酚）下，JM-1232（-）的松弛作用无显著差异。此外，所有这些作用都不依赖于功能性内皮的存在。氟马西尼能抑制JM-1232（-）对去甲肾上腺素预缩GEA的血管松弛作用，而纳洛酮不能抑制。结论：JM-1232（-）对人GEA平滑肌具有剂量依赖性松弛作用，这种作用不依赖于内皮细胞。在临床实践中达到的血浆浓度范围内，JM-1232（-）具有与咪达唑仑和异丙酚相似的血管松弛作用。氟马西尼抑制了JM-1232（-）诱导的血管松弛，表明JM-1232（-）诱导的血管松弛是通过外周苯二氮卓受体激活在GEA中发生的。(C) 2011爱思唯尔公司版权所有。
Objective: To investigate the effects of JM-1232(-) on norepinephrine (10(-6) mol/L)- and high K+ (40 mmol/L)-induced contractions in isolated human gastroepiploic arteries (GEA), and to compare them with the effects of midazolam and propofol. In addition, to investigate whether the benzodiazepine-receptor antagonist, flumazenil, or mu-opioid-receptor antagonist, naloxone, influenced the vascular effects of JM-1232(-).Design: An in vitro experimental study.Setting: University laboratory.Participants: GEA segments were used from 69 patients undergoing coronary artery bypass graft surgery.Measurements and Main Results: JM-1232(-) produced dose-dependent relaxation effects in the rings. Although these effects of JM-1232(-) were greater than those of midazolam and propofol at high concentrations (10(-5)-10(-4) mol/L), there were no significantly different relaxation effects at the clinical concentrations of 3 x 10(-6) mol/L JM-1232(-),3 x 10(-6) mol/L midazolam, and 1 x 10(-5) mol/L propofol. In addition, all these effects were independent of the presence of a functional endothelium. Vasorelaxation induced by JM-1232(-) on norepinephrine-preconstricted GEA was inhibited by flumazenil, but not by naloxone.Conclusions: These results indicate that JM-1232(-) dose-dependently relaxes smooth muscle in human GEA, this effect being independent of the endothelium. Within the ranges of plasma concentrations achieved in clinical practice, JM-1232(-) had similar vasorelaxation effects to midazolam and propofol. JM-1232(-)-induced vasorelaxation was inhibited by flumazenil, indicating that JM-1232(-)-induced vasorelaxation occurred via peripheral benzodiazepine receptor activation in the GEA. (C) 2011 Elsevier Inc. All rights reserved.