Evidence for an essential role of cyclooxygenase-2 as a mediator of the late phase of ischemic preconditioning in mice.
Recent studies have demonstrated that cyclooxygenase-2 (COX-2) is an essential mediator of the cardioprotective effects of the late phase of ischemic preconditioning (PC) in rabbits. The goal of this study was to determine whether COX-2 also plays an essential role in late PC in the mouse. B6129F2/J mice underwent a 30-min coronary occlusion followed by 24 h of reperfusion. Administration of the COX-2 selective inhibitor, NS-398, 30 min prior to the 30-min occlusion (5 mg/kg i.p.) had no appreciable effect on infarct size compared with untreated controls (58.8 +/- 2.1%, vs. 58.8 +/- 4.3% of the risk region, respectively). When mice were preconditioned with six cycles of 4-min coronary occlusion/4-min reperfusion 24 h prior to the 30-min occlusion, infarct size was markedly reduced (19.3 +/- 3.4%), indicating a late PC effect. The protective effect of late PC was completely abrogated by administration of NS-398 30 min before the 30-min coronary occlusion (67.7 +/- 3.0%), but not by administration of vehicle alone (23.6 +/- 3.7%). These results indicate that COX-2 mediates the late phase of ischemic PC in the mouse and imply that the role of this enzyme in cardioprotection is not species-specific.
Guo
Y
Y
University of Louisville, Division of Cardiology, Kentucky 40292, USA.
Bao
W
W
Wu
W J
WJ
Shinmura
K
K
Tang
X L
XL
Bolli
R
R
D000818:Animals; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D006321:Heart / Q000187:drug effects; D019194:Ischemic Preconditioning; D007527:Isoenzymes / Q000502:physiology*; D051379:Mice; D008815:Mice, Inbred Strains; D009203:Myocardial Infarction / Q000473:pathology; D009206:Myocardium / Q000473:pathology; D009578:Nitrobenzenes / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000502:physiology*; D013449:Sulfonamides / Q000494:pharmacology
D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D009578:Nitrobenzenes; D013449:Sulfonamides; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases