Interaction of eicosanoids and nitric oxide in renal reperfusion injury

Both the eicosanoids and nitric oxide are known to play an important role in the pathogenesis of postischemic injury. Recent evidence has suggested that the generation of each may affect the other via a feedback loop. This was investigated in an experimental model of renal warm ischemia reperfusion injury.

Rats underwent bilateral renal warm ischemia (15-60 min) then reperfusion (20 or 80 min) followed by a unilateral nephrectomy to measure renal nitric oxide (as nitroxides) and eicosanoids. Renal function was measured on days 2 and 7 prior to terminal nephrectomy for tissue analysis.

Vasodilator eicosanoids (6-KPGF1alpha and PGE2) fell on reperfusion in line with the duration of warm ischemia with a concomitant rise in the vasoconstrictor TxA2. The ratio of vasodilator to vasoconstrictor eicosanoids 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 reperfusion demonstrating an inverse correlation with the eicosanoid ratio (r2=0.86). Renal function was impaired at both day 2 and day 7 and showed a positive correlation with the eicosanoid ratio (r2=0.67 and 0.62, respectively).

Renal warm ischemic injury is associated with a progressive fall in the ratio of vasodilator-to-vasoconstrictor eicosanoids from early in reperfusion through to day seven although nitric oxide was elevated throughout the same period. There was no evidence of coinduction of nitric oxide synthase and cyclooxygenase in this model.