{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T22:18:33Z","timestamp":1775600313767,"version":"3.50.1"},"reference-count":40,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2021,4,20]],"date-time":"2021-04-20T00:00:00Z","timestamp":1618876800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","award":["UIDB\/00215\/2020"],"award-info":[{"award-number":["UIDB\/00215\/2020"]}]},{"name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","award":["UIDP\/00215\/2020"],"award-info":[{"award-number":["UIDP\/00215\/2020"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomedicines"],"abstract":"<jats:p>Mineralocorticoid receptor antagonists (MRAs) are a class of anti-hypertensive drugs that act by blocking aldosterone action. The aim of this study was to evaluate whether the MRAs spironolactone and eplerenone influence adrenal cortical physiology and morphology. Spontaneous hypertensive rats (SHR, n = 18) and normotensive rats (WKY, n = 18) were randomly exposed to a daily dose of spironolactone (n = 6), eplerenone (n = 6), or no drug (n = 6) over 28 days. After that, aldosterone, corticosterone, and 11-deoxycorticosterone plasma concentrations were quantified. Adrenal glands were subjected to morphological analysis to assess lipid droplets content, capsular width, cell proliferation, and steroidogenic proteins expression. The adrenal cortex in untreated SHR showed higher lipid droplet content as than in WKY. In SHR, MRA treatment was associated with higher circulating aldosterone levels and Ki-67 expression in aldosterone-secreting cells. In WKY, the only difference observed after MRA spironolactone treatment was a narrower capsule. There was no difference in abundance of steroidogenic enzyme between groups. In conclusion, MRAs modify adrenal gland function and morphology in SHR. The effects observed within the adrenal glomerulosa with aldosterone-secreting cell proliferation and higher circulating aldosterone levels suggests that MRA treatment provokes activation of the renin angiotensin system. The prognostic value of hyperaldosteronism secondary to MRAs blockade requires further investigation.<\/jats:p>","DOI":"10.3390\/biomedicines9040441","type":"journal-article","created":{"date-parts":[[2021,4,20]],"date-time":"2021-04-20T13:58:04Z","timestamp":1618927084000},"page":"441","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Mineralocorticoid Receptor Antagonists Eplerenone and Spironolactone Modify Adrenal Cortex Morphology and Physiology"],"prefix":"10.3390","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6947-4560","authenticated-orcid":false,"given":"Sofia","family":"Pereira","sequence":"first","affiliation":[{"name":"Department of Anatomy and Unit for Multidisciplinary Biomedical Research (UMIB) of Instituto de Ci\u00eancias Biom\u00e9dicas Abel Salazar (ICBAS), University of Porto, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9081-3184","authenticated-orcid":false,"given":"Liliana","family":"Carvalho","sequence":"additional","affiliation":[{"name":"Department of Experimental Biology, Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal"}]},{"given":"Madalena","family":"Costa","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Unit for Multidisciplinary Biomedical Research (UMIB) of Instituto de Ci\u00eancias Biom\u00e9dicas Abel Salazar (ICBAS), University of Porto, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9153-0773","authenticated-orcid":false,"given":"Armindo","family":"Melo","sequence":"additional","affiliation":[{"name":"Department of Environmental Health, National Institute of Health Dr. Ricardo Jorge, 4000-055 Porto, Portugal"},{"name":"Laborat\u00f3rio Associado Para a Qu\u00edmica Verde (LAQV\/REQUIMTE), University of Porto, 4050-313 Porto, Portugal"}]},{"given":"Isabel","family":"Ferreira","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio Associado Para a Qu\u00edmica Verde (LAQV\/REQUIMTE), University of Porto, 4050-313 Porto, Portugal"},{"name":"Laboratory of Bromatology and Hidrology, Department of Chemical Sciences, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal"}]},{"given":"Celso","family":"Gomez-Sanchez","sequence":"additional","affiliation":[{"name":"Endocrinology Section, G.V. (Sonny) Montgomery VA Medical Center, Montgomery, AL 36109, USA"},{"name":"Department of Medicine, University of Mississippi Medical Center, Jackson, MS 39216, USA"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0662-1831","authenticated-orcid":false,"given":"Mariana","family":"Monteiro","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Unit for Multidisciplinary Biomedical Research (UMIB) of Instituto de Ci\u00eancias Biom\u00e9dicas Abel Salazar (ICBAS), University of Porto, 4050-313 Porto, Portugal"}]},{"given":"Gavin","family":"Vinson","sequence":"additional","affiliation":[{"name":"The School of Biological and Chemical Sciences, Queen Mary University of London, London E1 4NS, UK"}]},{"given":"Duarte","family":"Pignatelli","sequence":"additional","affiliation":[{"name":"Department of Experimental Biology, Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal"},{"name":"Cancer Signalling &amp; Metabolism Group, Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, University of Porto, 4200-135 Porto, Portugal"},{"name":"Cancer Signalling &amp; Metabolism Group, Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), 4200-135 Porto, Portugal"},{"name":"Department of Endocrinology, Hospital S. Jo\u00e3o, 4200-319 Porto, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2021,4,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1677\/joe.1.06017","article-title":"The new biology of aldosterone","volume":"186","author":"Connell","year":"2005","journal-title":"J. Endocrinol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"T125","DOI":"10.1530\/JOE-16-0600","article-title":"30 Years of the Mineralocorticoid Receptor: Mineralocorticoid receptor antagonists: 60 years of research and development","volume":"234","author":"Kolkhof","year":"2017","journal-title":"J. Endocrinol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"403","DOI":"10.2147\/VHRM.S138599","article-title":"Managing resistant hypertension: Focus on mineralocorticoid-receptor antagonists","volume":"13","author":"Modolo","year":"2017","journal-title":"Vasc. 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