The role of arachidonic acid metabolites in the subtype classification and pathogenesis of primary aldosteronism

Primary aldosteronism (PA) is a common form of secondary hypertension with a complex diagnostic process and incompletely understood pathogenesis. In this controlled cross-sectional study, metabolomic profiling of 37 patients with bilateral PA, 38 with unilateral PA, and 20 with essential hypertension (EH) revealed that the most prominent metabolic difference lies in lipid metabolism, particularly arachidonic acid (AA) metabolism. We identified a panel of AA metabolites that improved PA subtyping. Additionally, levels of most AA metabolites were markedly reduced in PA patients after curative adrenal ablation. Mechanistically, treatment with AA enhanced the uptake of calcium ions and stimulated the proliferation and migration of adrenal cortical cells, with increased expressions of aldosterone synthase CYP11B2 and the calcium ion channel transient receptor potential canonical 3 (TRPC3). Furthermore, an inhibitor of TRPC3, pyr3, blocked these effects of AA. These findings elucidate the role of AA metabolites in PA pathogenesis and highlight them as potential targets for therapeutic intervention.