Interaction of eicosanoids and nitric oxide in renal reperfusion injury

Background. Both the eicosanoids and nitric oxide are known to play an impo rtant role in the pathogenesis of postischemic injury. Recent evidence has suggested that the generation of each may affect the other via a feedback l oop. This was investigated in an experimental model of renal warm ischemia reperfusion injury. Methods. Rats underwent bilateral renal warm ischemia (15-60 min) then repe rfusion (20 or 80 min) followed by a unilateral nephrectomy to measure rena l nitric oxide (as nitroxides) and eicosanoids. Renal function was measured on days 2 and 7 prior to terminal nephrectomy for tissue analysis. Results. Vasodilator eicosanoids (6-KPGF(1 alpha) and PGE(2)) fell on reper fusion in line with the duration of warm ischemia with a concomitant rise i n the vasoconstrictor TxA(2). The ratio of vasodilator to vasoconstrictor e icosanoids fell from 8.22 (2.3) in the control to 0.82 (0.1) in the 60-min warm ischemia group (P <0.01). Renal levels of nitroxides rose on reperfusi on demonstrating an inverse correlation with the eicosanoid ratio (r(2)=0.8 6). Renal function was impaired at both day 2 and day 7 and showed a positi ve correlation with the eicosanoid ratio (r(2)=0.67 and 0.62, respectively) . Conclusions. Renal warm ischemic injury is associated with a progressive fa ll in the ratio of vasodilator-to-vasoconstrictor eicosanoids from early in reperfusion through to day seven although nitric oxide was elevated throug hout the same period. There was no evidence of coinduction of nitric oxide synthase and cyclooxygenase in this model.