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Activation of calcium‐activated potassium (BKCa) channels prevents ischemia‐reperfusion‐induced leukocyte‐endothelial adhesive interactions
Author(s) -
Kalogeris Theodore John,
Wang Meifang,
Gaskin Frederick Spencer,
Yusof Mozow,
Wang Qun,
Korthuis Ronald J.
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a1220-d
Subject(s) - intravital microscopy , ischemia , ischemic preconditioning , chemistry , reperfusion injury , pharmacology , superior mesenteric artery , in vivo , inflammation , activator (genetics) , medicine , immunology , microcirculation , biology , receptor , microbiology and biotechnology
Activation of BK Ca channels plays a role in eliciting the infarct‐sparing effects of late ischemic preconditioning in animal models of myocardial ischemia‐reperfusion (I/R) injury. The aim of this study was to test whether pharmacologic preconditioning with the selective BK Ca channel activator, NS‐1619, (NS‐1619‐PC) would initiate the development of an anti‐inflammatory phenotype in postcapillary venules such that these vessels fail to support leukocyte‐endothelial interactions on exposure to I/R 24 hrs later. To address this aim, C57BL6 mice were administered either NS‐1619 (ip, 0.1 mg/kg) or its vehicle (DMF). Twenty four h later, the superior mesenteric artery was occluded for 45 min followed by 60 min of reperfusion, then leukocyte rolling (LR) and adhesion (LA) were quantified in intestinal postcapillary venules using intravital microscopy. DMF injection alone had no effect on either LR or LA under both sham (no I/R) and I/R conditions. I/R induced large increases in LR and LA in DMF‐injected mice compared with non‐ischemic controls. These effects were largely abolished by NS‐1619‐PC. Thus, pharmacologic activation of BK Ca channels 24 hrs prior to an ischemic insult elicits an anti‐inflammatory phenotype in intestinal postcapillary venules which effectively prevents LR and LA on subsequent exposure to I/R. Supported by AA14945 and DK43785.