Soluble epoxide hydrolase inhibition reduces the cardiovascular consequences of renal ischemia-reperfusion

Ischemia-reperfusion (I/R) injury is an immediate complication of renal transplantation and a determinant of persistent allograft injury and related cardiovascular outcomes. Epoxyeicosatrienoic acids (EETs) are endothelium- derived hyperpolarizing factors with anti-inflammatory and vasodilator properties. The objective of our study was to evaluate the effects of t-AUCB, a pharmacological inhibitor of EETs degradation, on the shortand potential long-term consequences of renal I/R. C57Bl/6J mice were subjected to 30-min renal bilateral I/R, and subsequently received t-AUCB (15 mg/l PO) or vehicle. Kidney function and pathology were evaluated after 48 hours (h48), 28 days (d28) and 8 months (m8). Vascular function on isolated renal artery, and cardiac function were evaluated at d28 (echocardiography, invasive hemodynamics), and m8(echocardiography). Renal I/R produced severe renal failure at h48, and mild renal failure at d28 and m8, non significantly reduced by t-AUCB (plasma creatinine sham 5.0±1.7 μmol/l; d28 I/R 14.9±2.7; d28 I/R+t-AUCB 10.8±1.1; m8 I/R 6.6±1.2; m8 I/R+t-AUCB 7.0±1.3). Kidney histology revealed severe tubulointerstitial lesions at d28, reduced by t-AUCB (sham 0.3±0.1; I/R 1.5±0.2, p The author hereby declares no conflict of interest