{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T09:00:14Z","timestamp":1790758814444,"version":"4.1.0"},"reference-count":21,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T00:00:00Z","timestamp":1790726400000},"content-version":"vor","delay-in-days":33,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100018989","name":"FOundation for advanced Research In hypertension and CArdiovascular disease","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100018989","id-type":"DOI","asserted-by":"publisher"}]},{"name":"FORICA"},{"DOI":"10.13039\/100018800","name":"ETS","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100018800","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Hypertension and Vascular Biology"},{"name":"ARHYVAB"},{"DOI":"10.13039\/501100003500","name":"University of Padua","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003500","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000780","name":"European Union's Horizon 2020 research and innovation program","doi-asserted-by":"publisher","award":["954798"],"award-info":[{"award-number":["954798"]}],"id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,8,28]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Primary aldosteronism (PA), the most common curable form of hypertension, is frequently caused by aldosterone-producing adenomas (APAs) harbouring KCNJ5 mutations that render aldosterone synthesis sensitive to macrolides in vitro. This study aimed to evaluate whether a single dose of roxithromycin reduces plasma aldosterone concentration (PAC) and blood pressure (BP) in patients with KCNJ5-mutated APA, and to characterize the haemodynamic effects of macrolides in mice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design<\/jats:title>\n                    <jats:p>Prospective, within-patient pharmacologic challenge.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>At the specialized Hypertension Center, University of Padua, eligible consecutive hypertensive patients screened for PA underwent a pharmacologic challenge with a single oral dose of roxithromycin to investigate the within-patient changes in PAC, active renin, cortisol, and BP.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Among 373 challenged patients, 18 had KCNJ5 (G151R or L168R)-mutated APA, 25 had wild-type APA, and 307 had no PA. Roxithromycin reduced PAC (P &amp;lt; .001) only in APA with KCNJ5 mutation, albeit it did not lower BP values. However, it produced a small BP decrease in non-PA hypertensive patients. Mouse studies showed that this BP lowering can be due to macrolide-induced attenuation of angiotensin II actions involving enhancement of endothelium- and nitric oxide\u2013dependent vasodilation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The selective suppression of aldosterone secretion with roxithromycin in KCNJ5-mutated APA in vivo, which aligns with ex vivo mechanistic data, can represent a functional marker of KCNJ5 mutations and could help guide precision subtyping of PA patients. Macrolides also exhibit an aldosterone-independent antihypertensive effect in non-PA patients, which involves nitric oxide\u2013dependent vasodilation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/ejendo\/lvag161","type":"journal-article","created":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T14:22:32Z","timestamp":1787926952000},"page":"470-477","source":"Crossref","is-referenced-by-count":0,"title":["Macrolide-induced aldosterone suppression as a functional marker of KCNJ5-mutated aldosterone-producing adenoma: a proof-of-concept clinical and experimental study (MAPA study)"],"prefix":"10.1093","volume":"195","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7963-0931","authenticated-orcid":false,"given":"Gian Paolo","family":"Rossi","sequence":"first","affiliation":[{"name":"Internal & Emergency Medicine and Hypertension Center, University of Padua , Padua 35128 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Madrid and Instituto de Investigaci\u00f3n Hospital Universitario La Paz (IdiPaz) , 28029 Madrid ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4687-8033","authenticated-orcid":false,"given":"Giulio","family":"Ceolotto","sequence":"additional","affiliation":[{"name":"Internal & Emergency Medicine and Hypertension Center, University of Padua , Padua 35128 ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Zanotti","sequence":"additional","affiliation":[{"name":"Department of Molecular Sciences, University of Padua , Padua 35100 ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto","family":"Padrini","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology, Department of Medicine \u2013 DIMED, University of Padua , Padua 35100 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