Influence of renal lipoxygenase activity on the renal vascular response to arachidonic acid

Studies were undertaken to clarify the effects of close arterial injections of arachidonic acid (AA) on renal blood flow in anesthetized dogs. In some dogs, injection of 4 mg of AA into the renal artery produces only renal vasodilation, whereas in other dogs similar injections lead to biphasic responses in which vasodilation is preceded by transient vasoconstriction. In the present experiments the cyclooxygenase inhibitor ibuprofen blocked vasodilator responses, suggesting that these were mediated by conversion of the precursor to prostaglandins. However, ibuprofen did not block the constrictor phase of the response in those animals that exhibited biphasic responses, suggesting that this phase was not mediated by prostaglandins. Administration of agents that inhibit lipoxygenase and cytochrome P-450 enzymes blocked the constrictor phase, suggesting that this portion of the responses was associated with conversion of the precursor to hydroxylated eicosanoids. An additional observation from these studies was that the frequency of occurrence of biphasic responses to intrarenal AA injections in water-deprived dogs was significantly greater than that found in non-water-deprived dogs, suggesting a connection between hydration state and the activity of nonprostaglandin pathways for AA metabolism in the canine kidney.