Molecular changes in the cytochrome P450 4A isoforms in the Sprague Dawley rat kidney following ischemia/reperfusion

20‐HETE is a major eicosanoid in the kidney, but little is known about the molecular regulation of the enzymes that produce this molecule in the kidney following ischemia‐reperfusion (I/R) injury. We designed the following study to determine the changes in the cytochrome P450 4A isoforms, specifically CYP4A1, 4A2, 4A3, and 4A8, following I/R in uninephrectomized Sprague Dawley (SD) rats. SD rats were sham‐operated or exposed to ischemia by clamping of renal artery and vein for 45 minutes, and then reperfused for 1, 3 or 7 days. Medullary CYP4A protein levels determined by Western blot analysis started to decrease 1 day after reperfusion and reduction levels reached to ~10% (P<0.01; n=5) of the control levels at day 3 post‐I/R. No changes in the cortical protein levels were detected. To determine the mRNA changes in the medulla, quantitative RT‐PCR was performed. CYP4A2, CYP4A3 and CYP4A8 mRNA levels decreased significantly following I/R, and reached their nadir at day 3 post‐I/R between 74–93% (P<0.05). These findings would suggest that CYP4A isoforms are differentially regulated in the kidney following I/R and may have a possible role in mediating biological effects in response to this type of injury.