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Protective effect of 11,12‐epoxyeicosatrienoic acid in lung ischemia‐reperfusion injury
Author(s) -
Townsley Mary,
Barnes Sue,
Morisseau Christophe,
Hammock Bruce,
King Judy
Publication year - 2009
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.23.1_supplement.763.10
Subject(s) - blockade , chemistry , cell adhesion molecule , reperfusion injury , ischemia , lung , pharmacology , glibenclamide , ischemic preconditioning , endocrinology , medicine , biochemistry , receptor , immunology , diabetes mellitus
Epoxyeicosatrienoic acids (EETs) are protective in myocardial and brain ischemia, an effect variously attributed to activation of K ATP channels or blockade of adhesion molecule expression. This study addressed whether EETs would attenuate the increase in permeability induced by 45 min ischemia‐30 min reperfusion (IR) in isolated, buffer‐perfused rat lungs. The filtration coefficient (K f ), a sensitive index of endothelial permeability, increased 10.5±2.5‐fold (mean±SE) after IR alone (p<0.05), but not in time controls. Blockade of endogenous EET degradation with dicyclohexylurea (50 ?M) or compound 950 (100 ?M) did not significantly attenuate the response to IR (K f increased 5.5±0.9‐fold). In lungs treated with 11,12‐EET (300 nM) at reperfusion, K f only increased 2.5±0.6‐fold (p<0.05 vs IR). 14,15‐EET (300 nM) administered at reperfusion had no significant benefit. The beneficial effect of 11,12‐EET was not prevented by blockade of K ATP channels (glibenclamide, 10 μM) nor by blockade of TRPV4 (ruthenium red, 3 μM). Finally, 11,12‐EET‐dependent alteration in adhesion molecules expression is unlikely to explain its beneficial effect, since the expression of the adhesion molecules VCAM and ICAM in lung after IR was similar to that in time controls. We conclude that 11,12‐EET has benefit in the setting of lung IR, though understanding its mechanism will require further study. Supported by HL067461.