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AICAR Preconditioning Prevents Postischemic Leukocyte Rolling and Adhesion: Role of K ATP Channels and Heme Oxygenase
Author(s) -
GASKIN F. SPENCER,
KAMADA KAZUHIRO,
YUSOF MOZOW,
DURANTE WILLIAM,
GROSS GARRETT,
KORTHUIS RONALD J.
Publication year - 2009
Publication title -
microcirculation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.793
H-Index - 83
eISSN - 1549-8719
pISSN - 1073-9688
DOI - 10.1080/10739680802355897
Subject(s) - heme oxygenase , chemistry , enos , heme , nitric oxide synthase , ampk , potassium channel , nitric oxide , ischemia , protein kinase a , medicine , endocrinology , biochemistry , phosphorylation , enzyme , biology , organic chemistry
Objective: We previously demonstrated that pharmacologic activation of AMP‐activated protein kinase (AMPK) with 5‐aminoimidazole‐4‐carboxamide 1‐β‐D‐ribofuranoside (AICAR) 24 hours prior to (AICAR preconditioning; AICAR‐PC) ischemia/reperfusion (I/R) prevents postischemic leukocyte‐endothelial cell adhesive interactions (LEI) by a mechanism initiated by endothelial nitric oxide synthase (eNOS)‐dependent NO production during the period of AICAR‐PC. The major aim of this study was to examine the role of ATP‐sensitive potassium (K ATP ) channels and heme oxygenase as mediators of the antiadhesive effects of AICAR‐PC during I/R 24 hours later. Methods: Intravital fluorescence microscopy was used to quantify LEI in the small intestine of AICAR‐preconditioned C57BL/6J mice treated with K ATP channel or heme oxygenase inhibitors during I/R 24 hours after AICAR‐PC in separate experiments. Results: I/R induced marked increases in LEI relative to sham control mice, proadhesive responses that were prevented by AICAR‐PC 24 hours prior to I/R. The effects of AICAR‐PC to prevent postischemic LEI were abolished by K ATP channel or heme oxygenase inhibition during I/R. Discussion/Conclusion: Our results indicate that the antiadhesive effects of AICAR‐PC are mediated by K ATP channel‐ and heme oxygenase‐dependent mechanisms during I/R.