Action of arachidonic acid in ureteral-ligated kidney of the anesthetized canine: possible lipoxygenase activity

Abstract

In anesthetized dogs 48 h after unilateral ureteral ligation, intra-arterial injection of arachidonic acid produced a transient increase followed by a prolonged decrease of resistance in the ureterai-ligated kidney; whereas, in the control kidney, only the prolonged decrease in resistance was observed in response to arachidonate. Indomethacin blocked not only the arachidonate-induced renal efflux of both immunoreactive 6-keto-prostaglandin F1α and thromboxane B2 but also vasodilation in both kidneys, in contrast, the initial vasoconstriction in the obstructed kidney was not affected by pretreatment with the cyclo-oxygenase inhibitor. Infusion of 5,8,11,14-eicosatetraynoie acid, an inhibitor of lipoxygenase activity, into the ureteral-ligated kidney after indomethacin markedly reduced the initial vasoconstrictor response to arachidonate. These data demonstrate that vascular reactivity to arachidonic acid is altered in the ureteral-obstructed kidney and are consistent with the hypothesis that formation of lipoxygenase as well as cyclooxygenase derivatives may participate in the hemodynamic responses to arachidonic acid in this pathophysiologic model.