Impact of epoxyeicosatrienoic acids in lung ischemia-reperfusion injury.
OBJECTIVE
Epoxyeicosatrienoic acids (EETs) are protective in both myocardial and brain ischemia, variously attributed to activation of K(ATP) channels or blockade of adhesion molecule upregulation. In this study, we tested whether EETs would be protective in lung ischemia-reperfusion injury.


METHODS
The filtration coefficient (K(f)), a measure of endothelial permeability, and expression of the adhesion molecules vascular cell adhesion molecule (VCAM) and intercellular adhesion molecule (ICAM) were measured after 45 minutes ischemia and 30 minutes reperfusion in isolated rat lungs.


RESULTS
K(f) increased significantly after ischemia-reperfusion alone vs time controls, an effect dependent upon extracellular Ca(2+) although not on the EET-regulated channel TRPV4. Inhibition of endogenous EET degradation or administration of exogenous 11,12- or 14,-15-EET at reperfusion significantly limited the permeability response to ischemia-reperfusion. The beneficial effect of 11,12-EET was not prevented by blockade of K(ATP) channels nor by blockade of TRPV4. 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 ischemia-reperfusion was similar to that in controls.


CONCLUSIONS
EETs are beneficial in the setting of lung ischemia-reperfusion, when administered at reperfusion. However, further study will be needed to elucidate the mechanism of action.
Townsley
Mary I
MI
Department of Physiology, Center for Lung Biology, University of South Alabama, Mobile, AL 36688, USA. mtownsley@usouthal.edu
Morisseau
Christophe
C
Hammock
Bruce
B
King
Judy A
JA
D015126:8,11,14-Eicosatrienoic Acid / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects; D015815:Cell Adhesion Molecules / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D008168:Lung / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism; D055370:Lung Injury / Q000188:drug therapy / Q000378:metabolism / Q000517:prevention & control*; D051381:Rats; D015427:Reperfusion Injury / Q000188:drug therapy / Q000378:metabolism / Q000517:prevention & control*; D050916:TRPV Cation Channels / Q000378:metabolism; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
D015815:Cell Adhesion Molecules; D050916:TRPV Cation Channels; C486577:Trpv4 protein, rat; D019010:Vascular Cell Adhesion Molecule-1; C046783:11,12-epoxy-5,8,14-eicosatrienoic acid; C046782:14,15-epoxy-5,8,11-eicosatrienoic acid; D015126:8,11,14-Eicosatrienoic Acid