Abstract P2024: Treatment of Primary Hyperaldosteronism Increases Plasma Epoxyeicosatrienoic Acids

Abstract

Epoxyeicosatrienoic acids (EETs) are lipid signaling molecules formed from arachidonic acid by the action of CYP450s. EETs cause vasodilation, exert anti-inflammatory effects, and enhance insulin secretion and sensitivity. 14,15-DHET has been reported to be increased in patients with hyperaldosteronism, but the effects of aldosteronism on EETs and sEH activity are unknown. We tested the hypothesis that treatment of hyperaldosteronism would alter EET concentrations. We studied 9 patients with biochemically confirmed hyperaldosteronism before and after unilateral adrenalectomy (6) or treatment with a mineralocorticoid (MR) antagonist. Aldosterone decreased significantly from 20.4±15.2 to 6.2±3.7 ng/mL following treatment, but cortisol did not change. Circulating total EET concentrations increased from 11.9±5.9 to 18.5±12.6 nM with treatment of primary hyperaldosteronism. Among the regioisomers of EETs, 14,15-EET significantly increased after treatment, whereas 11,12-EET and 8,9 EET did not change significantly ( Figure ; • adrenalectomy, ○ MR antagonist). EET concentrations increased in patients treated with an MR antagonist as well as those treated by surgical resection. Total DHET concentrations and specific regioisomers of DHET did not change significantly with treatment. Circulating total EETs (r=-0.52, p =0.026), 14,15-EET (-0.56, p =0.015) and 11,12-EET (r=-0.48, p =0.042) correlated inversely with aldosterone. We report for the first time that circulating EET concentrations increase following treatment of primary hyperaldosteronism.