Abstract

Several actions of angiotensin II have been linked to metabolism of arachidonic acid by lipoxygenases. To evaluate the importance of this interaction intrarenally we tested the effect of three different lipoxygenase inhibitors, BW755c (50 microM), a dual lipoxygenase-cyclooxygenase inhibitor, MK447 (200 microM), a nonselective lipoxygenase inhibitor which can stimulate cyclooxygenase, and baicalein (1 microM), a highly selective 12-lipoxygenase inhibitor, on angiotensin II-evoked hemodynamic changes in the rat isolated kidney, perfused with oncotic agents. Kidneys were pretreated with indomethacin (10 microM) to exclude participation of cyclooxygenase-dependent arachidonate products. Renal perfusion pressure was kept constant at 90 mm Hg by continuous adjustments in perfusate flow rate. Inhibition of cyclooxygenase alone produced a transient potentiation of the vasoconstrictor response to angiotensin II without altering GFR. On the other hand, the lipoxygenase inhibitors attenuated the angiotensin II-induced increase in renal vascular resistance by approximately 50% and promoted an increase in GFR above that of kidneys infused with angiotensin II in the presence of only indomethacin. Base-line values were essentially unchanged by lipoxygenase inhibition. Furthermore, the vasoconstrictor response to the thromboxane/endoperoxide agonist U46619 was unaffected. We conclude that products of the lipoxygenase pathway, arising within the kidney, contribute to the renal hemodynamic effects of angiotensin II.