Preventive Effects of Exenatide on Endothelial Dysfunction Induced by Ischemia-Reperfusion Injury via KATP Channels

OBJECTIVE—The purpose of this study was to evaluate whether exenatide administration can prevent impairment in endothelium-dependent vasodilatation induced by ischemia-reperfusion (IR) injury and whether this effect is mediated by KATP channel opening. METHODS AND RESULTS—In a double-blind, placebo-controlled, crossover design, 20 volunteers were randomly assigned to 2 groupssubcutaneous exenatide (10 μg) or placebo administration. At 30 minutes after the study drug administration, endothelium-dependent flow-mediated dilatation (FMD) of the radial artery was measured before and after IR (15 minutes of ischemia at the level of the brachial artery followed by 15 minutes of reperfusion) injury. Seven days later, both groups were crossed over and received the other treatment (ie, placebo or exenatide) and underwent the same protocol. Pre-IR radial artery diameter, FMD, and baseline radial artery diameter after IR injury were similar between 2 groups (P=no significant difference). After placebo administration, IR significantly blunted FMD (before IR12.0±6.23%; after IR4.6±3.57%, P=0.02). Exenatide prevented this impairment (FMD before IR15.0±7.14%; FMD after IR15.0±5.96%, P=no significant difference; P