{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T15:37:22Z","timestamp":1789141042382,"version":"build-2803163510"},"reference-count":53,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"12","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Hypertension"],"published-print":{"date-parts":[[2024,12]]},"abstract":"\n BACKGROUND:<\/jats:title>\n \n Primary aldosteronism (PA), the most common curable salt-dependent form of arterial hypertension, features renal K\n +<\/jats:sup>\n loss and enhanced Na\n +<\/jats:sup>\n reabsorption. We investigated whether the electrolyte, water, and TonEBP (tonicity-responsive enhancer binding protein)\/\n NFAT5<\/jats:italic>\n (nuclear factor of activated T cells 5) content is altered in the skin of patients with PA and corrected by surgical cure.\n <\/jats:p>\n <\/jats:sec>\n \n METHODS:<\/jats:title>\n \n We obtained skin biopsies from 80 subjects: 49 consecutive patients with PA, optimally treated with a mineralocorticoid receptor antagonist; 6 essential hypertensives; and 25 normotensive controls. We measured Na\n +<\/jats:sup>\n , K\n +<\/jats:sup>\n , water content with atomic absorption spectroscopy after ashing, and\n NFAT5<\/jats:italic>\n mRNA with digital droplet polymerase chain reaction. The patients with PA were retested after adrenalectomy.\n <\/jats:p>\n <\/jats:sec>\n \n RESULTS:<\/jats:title>\n \n We discovered a higher dry weight of the skin biopsy specimen at surgery than at follow-up (\n P<\/jats:italic>\n <0.001) and a direct correlation with electrolyte and water content (all\n P<\/jats:italic>\n <0.01), indicating the need for dry weight adjustment of electrolyte and water data. Surgical cure of PA markedly increased skin dry weight\u2013adjusted K\n +<\/jats:sup>\n (from 1.14\u00b10.1 to 2.81\u00b10.27 \u00b5g\/mg;\n P<\/jats:italic>\n <0.001) and water content (from 2.92\u00b11.4 to 3.85\u00b10.23 mg\/mg;\n P<\/jats:italic>\n <0.001), but left dry weight\u2013adjusted skin Na\n +<\/jats:sup>\n content unaffected. In patients with PA at baseline,\n NFAT5<\/jats:italic>\n mRNA was higher (\n P<\/jats:italic>\n =0.031) than in normotensive controls and decreased after surgery (\n P<\/jats:italic>\n =0.035).\n <\/jats:p>\n <\/jats:sec>\n \n CONCLUSIONS:<\/jats:title>\n \n Despite mineralocorticoid receptor antagonist treatment ensuring normokalemia, the patients with PA had a skin cell K\n +<\/jats:sup>\n depletion that was corrected by adrenalectomy. The activated\n NFAT5<\/jats:italic>\n \/TonEBP pathway during mineralocorticoid receptor antagonist administration suggests enhanced skin Na\n +<\/jats:sup>\n lymphatic drainage and can explain the lack of overt skin Na\n +<\/jats:sup>\n accumulation in patients with PA. Its deactivation after surgical cure can account for the lack of skin Na\n +<\/jats:sup>\n decrease postadrenalectomy.\n <\/jats:p>\n <\/jats:sec>\n \n REGISTRATION:<\/jats:title>\n \n URL:\n https:\/\/www.clinicaltrials.gov<\/jats:ext-link>\n ; Unique identifier: NCT06090617.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1161\/hypertensionaha.124.23700","type":"journal-article","created":{"date-parts":[[2024,10,2]],"date-time":"2024-10-02T09:00:34Z","timestamp":1727859634000},"page":"2468-2478","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":5,"title":["Water and Electrolyte Content in Hypertension in the Skin (WHYSKI) in Primary Aldosteronism"],"prefix":"10.1161","volume":"81","clinical-trial-number":[{"clinical-trial-number":"nct06090617","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8543-9300","authenticated-orcid":true,"given":"Francesca","family":"Torresan","sequence":"first","affiliation":[{"name":"Endocrine Surgery Unit, Department of Surgery, Oncology, and Gastroenterology (F.T., M.I.)."},{"name":"ARHYVAB PhD program in Arterial Hypertension and Vascular Biology, Department of Medicine (F.T., F.B.R., I.C., B.C., E.K., T.M.S., M.I., G.-P.R.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-7533-4577","authenticated-orcid":true,"given":"Federico B.","family":"Rossi","sequence":"additional","affiliation":[{"name":"ARHYVAB PhD program in Arterial Hypertension and Vascular Biology, Department of Medicine (F.T., F.B.R., I.C., B.C., E.K., T.M.S., M.I., G.-P.R.)."},{"name":"Internal and Emergency Medicine Unit and Specialized Hypertension Centre, Department of Medicine, University of Padua, Italy (F.B.R., I.C., B.C., T.M.S., G.-P.R.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3885-7256","authenticated-orcid":true,"given":"Ilaria","family":"Caputo","sequence":"additional","affiliation":[{"name":"ARHYVAB PhD program in Arterial Hypertension and Vascular Biology, Department of Medicine (F.T., F.B.R., I.C., B.C., E.K., T.M.S., M.I., G.-P.R.)."},{"name":"Internal and Emergency Medicine Unit and Specialized Hypertension Centre, Department of Medicine, University of Padua, Italy (F.B.R., I.C., B.C., T.M.S., G.-P.R.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sofia","family":"Zanin","sequence":"additional","affiliation":[{"name":"Laboratory for Genetics of Mitochondrial Disorders, Imagine Institute, Universit\u00e9 Paris Cit\u00e9, Paris, France (S.Z.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brasilina","family":"Caroccia","sequence":"additional","affiliation":[{"name":"ARHYVAB PhD program in Arterial Hypertension and Vascular Biology, Department of Medicine (F.T., F.B.R., I.C., B.C., E.K., T.M.S., M.I., G.-P.R.)."},{"name":"Internal and Emergency Medicine Unit and Specialized Hypertension Centre, Department of Medicine, University of Padua, Italy (F.B.R., I.C., B.C., T.M.S., G.-P.R.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2023-0749","authenticated-orcid":true,"given":"Andrea","family":"Mattarei","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical and Pharmacological (A.M., M.P.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michela","family":"Paccagnella","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical and Pharmacological (A.M., 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