{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T08:31:02Z","timestamp":1786523462120,"version":"build-2736575974"},"reference-count":24,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T00:00:00Z","timestamp":1786492800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T00:00:00Z","timestamp":1786492800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Endocrinology"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Preclinical studies suggest a novel aldosterone regulation pathway: the mineralocorticoid receptor (MR) on the adrenal cortex is a part of an MR\u2010mediated ultra\u2010short feedback loop regulating aldosterone production. Activation of MR on the adrenal decreases aldosterone; blockade of the MR increases aldosterone. Whether this regulatory pathway exists in humans is unknown.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This was a double\u2010blinded, 3\u2010way crossover study of 23 healthy participants on a low sodium diet (10\u2009mEq\/day). Participants received three study drugs in random order: MR antagonist (eplerenone), MR agonist (fludrocortisone), and placebo. Study drugs were administered at 6:30AM on three separate days with 48\u2009h between each administration. After 90\u2009min, participants received sequential infusions of angiotensin\u2010II (ANGII) for 45\u2009min followed 60\u2009min later by cosyntropin for 45\u2009min. Aldosterone was measured before and after each infusion. Multi\u2010level mixed effects linear regression was used to analyze the data.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The change in aldosterone between baseline and post\u2010cosyntropin infusion was greater after treatment with eplerenone as compared to placebo (5.16\u2009\u00b1\u20092.01\u2009ng\/dL,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.01). There were no differences with fludrocortisone as compared to placebo. With ANGII stimulation, there were no differences in the change in aldosterone with either eplerenone or fludrocortisone versus placebo.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>In humans, MR antagonist treatment led to a greater increase in aldosterone in response to cosyntropin stimulation as compared to placebo, but not after ANGII stimulation. Future studies are needed to investigate the presence of a MR\u2010mediated ultra\u2010short feedback loop at the level of the adrenal gland regulating aldosterone production in humans.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Clinical Trial Registration Number<\/jats:title>\n                    <jats:p>NCT02871648<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/cen.70189","type":"journal-article","created":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T07:52:51Z","timestamp":1786521171000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Investigating a Mineralocorticoid Receptor Mediation of an Ultra\u2010Short Feedback Loop Regulating Aldosterone Production in Humans"],"prefix":"10.1111","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9105-7154","authenticated-orcid":false,"given":"Yan Emily","family":"Yuan","sequence":"first","affiliation":[{"name":"Division of Endocrinology, Diabetes and Hypertension, Brigham and Women's Hospital Harvard Medical School Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gail K.","family":"Adler","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Diabetes and Hypertension, Brigham and Women's Hospital Harvard Medical School Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernard","family":"Rosner","sequence":"additional","affiliation":[{"name":"Department of Biostatistics Harvard T.H. Chan School of Public Health Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annie Altman","family":"Merino","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Diabetes and Hypertension, Brigham and Women's Hospital Harvard Medical School Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ezgi Caliskan","family":"Guzelce","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Diabetes and Hypertension, Brigham and Women's Hospital Harvard Medical School Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gordon H.","family":"Williams","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Diabetes and Hypertension, Brigham and Women's Hospital Harvard Medical School Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan S.","family":"Williams","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Diabetes and Hypertension, Brigham and Women's Hospital Harvard Medical School Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea V.","family":"Haas","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Diabetes and Hypertension, Brigham and Women's Hospital Harvard Medical School Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,12]]},"reference":[{"issue":"25","key":"e_1_2_9_2_1","first-page":"2982","article-title":"Global Burden of Cardiovascular Diseases and Risk Factors, 1990\u20102019: Update From the GBD 2019 Study","volume":"76","author":"Roth G. 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