Atrial natriuretic peptide counteracts aldosterone secretion by preventing acute angiotensin II‐induced cAMP signalling

BACKGROUND AND PURPOSE: -signalling, respectively. Atrial natriuretic peptide (ANP) prevents excessive aldosterone secretion from adrenal zona glomerulosa (ZG) cells. ANP reduces ACTH-stimulated aldosterone by enhancing cAMP degradation through cGMP-stimulated phosphodiesterase (PDE2A). It is not known whether PDE2A also participates in counteracting AngII-induced aldosterone secretion. EXPERIMENTAL APPROACH: In this study, we established CRISPR/Cas9 based knockdown of PDE2A in primary ZG cells and measured aldosterone release and cAMP/protein kinase A (PKA) activity using ELISA and Förster resonance energy transfer (FRET) biosensors, respectively. KEY RESULTS: -activated adenylyl cyclase to increase cAMP levels and PKA activity, which were almost completely blocked by ANP via PDE2A. CONCLUSION AND IMPLICATION: ANP/cGMP signalling effectively counteracts acute AngII-induced aldosterone secretion by activating PDE2A, which degrades AngII-stimulated cAMP and prevents PKA activation. This novel signalling pathway could be a target for new aldosterone-reducing drugs.