{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T18:12:19Z","timestamp":1790791939252,"version":"4.1.0"},"reference-count":51,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T00:00:00Z","timestamp":1778544000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T00:00:00Z","timestamp":1778544000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["KU 1037\/14\u20101"],"award-info":[{"award-number":["KU 1037\/14\u20101"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["NI 1301\/7\u20101"],"award-info":[{"award-number":["NI 1301\/7\u20101"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012190","name":"Ministry of Science and Higher Education of the Russian Federation","doi-asserted-by":"publisher","award":["075\u201000263\u201025\u201000"],"award-info":[{"award-number":["075\u201000263\u201025\u201000"]}],"id":[{"id":"10.13039\/501100012190","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"abstract":"<jats:sec>\n                    <jats:title>Background and Purpose<\/jats:title>\n                    <jats:p>\n                      Aldosterone plays a key role in blood pressure and volume regulation. Enhanced aldosterone secretion contributes to cardiovascular and renal diseases. Therefore, inhibitors of aldosterone receptors and synthase are essential drugs for the treatment of hypertension and heart failure. Both adrenocorticotropic hormone (ACTH) and angiotensin II (AngII) acutely increase aldosterone release via cAMP and Ca\n                      <jats:sup>2+<\/jats:sup>\n                      \u2010signalling, respectively. Atrial natriuretic peptide (ANP) prevents excessive aldosterone secretion from adrenal zona glomerulosa (ZG) cells. ANP reduces ACTH\u2010stimulated aldosterone by enhancing cAMP degradation through cGMP\u2010stimulated phosphodiesterase (PDE2A). It is not known whether PDE2A also participates in counteracting AngII\u2010induced aldosterone secretion.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Experimental Approach<\/jats:title>\n                    <jats:p>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 F\u00f6rster resonance energy transfer (FRET) biosensors, respectively.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key Results<\/jats:title>\n                    <jats:p>\n                      We first showed that inhibition of AngII\u2010stimulated aldosterone by ANP is mediated by cGMP independently of AngII\u2010stimulated Ca\n                      <jats:sup>2+<\/jats:sup>\n                      \u2010transients. However, knockdown of PDE2A completely abolished the inhibitory effect of the ANP\/cGMP pathway on AngII\u2010stimulated aldosterone, suggesting a cAMP\u2010dependent mechanism. Indeed, depletion of intracellular cAMP by PDE4 overexpression or by adenylyl cyclase inhibition prevented AngII\u2010stimulated aldosterone. Strikingly, AngII acutely stimulated Ca\n                      <jats:sup>2+<\/jats:sup>\n                      \u2010activated adenylyl cyclase to increase cAMP levels and PKA activity, which were almost completely blocked by ANP via PDE2A.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion and Implication<\/jats:title>\n                    <jats:p>ANP\/cGMP signalling effectively counteracts acute AngII\u2010induced aldosterone secretion by activating PDE2A, which degrades AngII\u2010stimulated cAMP and prevents PKA activation. This novel signalling pathway could be a target for new aldosterone\u2010reducing drugs.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/bph.70502","type":"journal-article","created":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T07:26:56Z","timestamp":1778570816000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Atrial natriuretic peptide counteracts aldosterone secretion by preventing acute angiotensin II\u2010induced cAMP signalling"],"prefix":"10.1111","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3181-857X","authenticated-orcid":false,"given":"Sanika","family":"Mohagaonkar","sequence":"first","affiliation":[{"name":"Institute of Experimental Cardiovascular Research University Medical Center Hamburg\u2010Eppendorf  Hamburg Germany"},{"name":"Partner site Hamburg\/Kiel\/L\u00fcbeck German Center of Cardiovascular Research (DZHK)  Hamburg 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