Arachidonate metabolism in renal injury

In conclusion, the evidence to date demonstrates that the enhanced arachidonate metabolism seen in hydronephrosis is responsible for the pathophysiological alterations observed in this model of renal injury. The balance between vasodilating prostaglandins and the vasoconstrictor thromboxane A2 may be critical in determining blood flow to the obstructed kidney. The alterations in arachidonate metabolism in this pathophysiologic state appear to result from the invasion of macrophages and the proliferation of fibroblasts in the cortical interstitium. Additionally, the macrophage appears to be necessary for the expression of the enhanced hormone-stimulated arachidonate metabolism. We envision the temporal sequence of events in this model to be as follows: ureter obstruction causes a mechanical disruption and/or immunologic stimulus in the cortex, which triggers a regional inflammatory response resulting in the proliferation of interstitial cells and the invasion of mononuclear cells. The macrophages, which are in direct contact with fibroblasts, are capable of releasing a factor that stimulates fibroblast proliferation, cortical microsomal cyclooxygenase activity, and prostaglandin E2 release (i.e., intrinsic arachidonate metabolism). The enhanced thromboxane synthetase levels and thromboxane A2 appear to come from the macrophage. The prostaglandin E2 and thromboxane A2 released modulate vascular tone. Prostaglandin E2 may also serve as an inhibitor of macrophage function. Two other models of renal damage also exhibit marked enhancement of renal prostaglandin synthesis and induction of thromboxane production: renal venous occlusion (32) and glycerol-induced acute renal failure (3). The finding that several models of renal damage have definite quantitative and qualitative alterations in the prostaglandin cascade reflects the importance of this pathway in renal pathophysiology.