title: Preventive effects of exenatide on endothelial dysfunction induced by ischemia-reperfusion injury via KATP channels.
abstract: 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 K(ATP) channel opening.
  
  
  RESULTS
  In a double-blind, placebo-controlled, crossover design, 20 volunteers were randomly assigned to 2 groups: subcutaneous 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 IR: 12.0±6.23%; after IR: 4.6±3.57%, P=0.02). Exenatide prevented this impairment (FMD before IR: 15.0±7.14%; FMD after IR: 15.0±5.96%, P=no significant difference; P<0.001 compared with placebo). In a separate protocol, this protective effect was completely abolished by pretreatment with glibenclamide (glyburide, 5 mg), a blocker of K(ATP) channels (n=7; FMD before IR: 12.0±2.2%; after IR: 3.2±2.1%, P<0.001).
  
  
  CONCLUSIONS
  The present study demonstrates that subcutaneous exenatide protects IR-induced endothelial dysfunction through opening of K(ATP) channels in human IR injury model.
authors.affiliation: Division of Cardiovascular, Department of Internal Medicine, Kyung Hee University Hospital, Kyung Hee University, #1 Hoegi-Dong, Dongdaemoon-Gu, Seoul 130-702, Korea.
authors.forename: Sang Jin
authors.initials: SJ
authors.lastname: Ha
authors.forename: Weon
authors.initials: W
authors.lastname: Kim
authors.forename: Jong Shin
authors.initials: JS
authors.lastname: Woo
authors.forename: Jin Bae
authors.initials: JB
authors.lastname: Kim
authors.forename: Soo Joong
authors.initials: SJ
authors.lastname: Kim
authors.forename: Woo-Shik
authors.initials: WS
authors.lastname: Kim
authors.forename: Myeong Kon
authors.initials: MK
authors.lastname: Kim
authors.forename: Xian Wu
authors.initials: XW
authors.lastname: Cheng
authors.forename: Kwon Sam
authors.initials: KS
authors.lastname: Kim
mesh_terms: D000328:Adult; D001916:Brachial Artery / Q000503:physiopathology; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000503:physiopathology*; D000077270:Exenatide; D005542:Forearm / Q000098:blood supply; D005905:Glyburide / Q000494:pharmacology; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D007279:Injections, Subcutaneous; D054086:KATP Channels / Q000187:drug effects / Q000502:physiology*; D010455:Peptides / Q000008:administration & dosage / Q000494:pharmacology*; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015427:Reperfusion Injury / Q000150:complications*; D014664:Vasodilation / Q000502:physiology; D014688:Venoms / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D007004:Hypoglycemic Agents; D054086:KATP Channels; D010455:Peptides; D026902:Potassium Channel Blockers; D014688:Venoms; D000077270:Exenatide; D005905:Glyburide