Angiotensin Feedback Inhibition on Renin Is Expressed Via the Lipoxygenase Pathway*

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Abstract
Angiotensin II (All) action on adrenal and smooth muscle cells is mediated via mechanisms that include changes in calcium flux and phosphoinositide hydrolysis. Phosphoinositide metabolism results in the release of arachidonic acid, a precursor of both the cyclooxygenase (CO) and lipoxygenase (LO) pathway. The effects of both LO and CO inhibitors on All action were studied using both static incubations and perifusions of rat renal cortical slices. 12-Hydroperoxyeicosatetraenoic acid and its stable metabolite 12-hydroxyacid mimicked the inhibitory actions of All on renin. A specific CO blocker did not alter All inhibition of renin and a 5-LO blocker U60.257 was also ineffective, whereas the LO blockers BW755c, phenidone, and baicalein all eliminated or interfered with the action of All on renin. All inhibition in the presence of a LO blocker was restored by adding nanomolar concentrations of 12-hydroperoxyeicosatetraenoic acid. LO inhibitors were specific for blocking All, as they did not interfere with potassium (K+)- induced renin inhibition. These results imply that 12 and/or 15 products of the LO pathway are involved in All action. (Endocrinology122: 1277–1281, 1988)