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The Early Phase of Preconditioning is Abrogated by COX‐2 Inhibition, but not by a Specific Prostaglandin Receptor Antagonist
Author(s) -
Booth Erin A,
Lucchesi Benedict R
Publication year - 2008
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.22.1_supplement.1130.5
Subject(s) - antagonist , ischemic preconditioning , nimesulide , downregulation and upregulation , prostaglandin , ischemia , medicine , pharmacology , receptor antagonist , receptor , endocrinology , chemistry , biochemistry , gene
COX‐2 is an important mediator of cardiovascular protection after ischemia and reperfusion and is essential for ischemic preconditioning (PC), mediated by the synthesis of PGE 2 and/or PGI 2 . Recently, the importance of the PGI 2 in the late phase of ischemic preconditioning has been established. The present study was designed to determine the contribution of PGI 2 to the early phase of ischemic preconditioning. Male New Zealand white rabbits were administered the prostaglandin receptor (IP) antagonist RO3244794 (3mg/kg), nimesulide (5mg/kg), or vehicle thirty minutes prior to PC, 30 minutes of ischemia and 4 hours of reperfusion. PC reduced myocardial infarct size as a percent of area at risk (12.0 +/− 2.2 vs. control 42.3 +/− 2.9; P < 0.001) and treatment with the COX‐2 inhibitor nimesulide abolished the protective effect (41.0 +/− 2.7). Surprisingly, treatment with the IP receptor antagonist had no effect on PC (17.0 +/− 3.1; P < 0.001 vs. control). The data suggest that COX‐2 does not protect the myocardium from the early phase of preconditioning through the production of PGI 2 . These results differ from those seen in the late phase of PC, where RO3244794 abrogated the protective effects of PC, suggesting that the upregulation of COX‐2 differentially modulates protection in the early and late phases of ischemic preconditioning.