{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,20]],"date-time":"2025-10-20T10:28:53Z","timestamp":1760956133907,"version":"build-2065373602"},"reference-count":64,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2021,12,8]],"date-time":"2021-12-08T00:00:00Z","timestamp":1638921600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001711","name":"Swiss National Science Foundation","doi-asserted-by":"publisher","award":["31003A-182478\/1"],"award-info":[{"award-number":["31003A-182478\/1"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Center of Competence in Research (NCCR)","award":["N-403-07-23"],"award-info":[{"award-number":["N-403-07-23"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Mutations within the glucocorticoid receptor (GR) gene locus lead to glucocorticoid resistance which is characterized by several clinical symptoms such as adrenal gland hyperplasia and salt-sensitive hypertension, although the underlying mechanisms are still unknown. We studied GR haploinsufficient (GR+\/\u2212) Sprague Dawley rats which, on a standard diet, showed significantly increased plasma aldosterone and corticosterone levels and an adrenocortex hyperplasia accompanied by a normal systolic blood pressure. Following a high salt diet, these rats developed salt-sensitive hypertension and maintained elevated enzyme-soluble epoxide hydrolase (sEH) in adrenal glands, while sEH was significantly decreased in wild-type rats. Furthermore, GR+\/\u2212 rats showed dysregulation of the equilibrated linoleic and arachidonic acid pathways, with a significant increase of less active metabolites such as 8,9-DiHETrE. In Sprague Dawley rats, GR haploinsufficiency induced steroid disturbances, which provoked hypertension only in combination with high salt intake, which was accompanied by disturbances in sEH and fatty acid metabolism. Our results suggest that sEH inhibition could be a potential target to treat hypertension in patients with GR haploinsufficiency.<\/jats:p>","DOI":"10.3390\/ijms222413218","type":"journal-article","created":{"date-parts":[[2021,12,10]],"date-time":"2021-12-10T02:07:18Z","timestamp":1639102038000},"page":"13218","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Salt-Sensitive Hypertension in GR+\/\u2212 Rats Is Accompanied with Dysregulation in Adrenal Soluble Epoxide Hydrolase and Polyunsaturated Fatty Acid Pathways"],"prefix":"10.3390","volume":"22","author":[{"given":"Paul-Emmanuel","family":"Vanderriele","sequence":"first","affiliation":[{"name":"Department of Biomedical Science, University of Lausanne, 1015 Lausanne, Switzerland"},{"name":"National Center of Competence in Research Kidney.CH, 8057 Z\u00fcrich, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qing","family":"Wang","sequence":"additional","affiliation":[{"name":"Division of Nephrology and Hypertension, Lausanne University Hospital (CHUV), 1015 Lausanne, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anne-Marie","family":"M\u00e9rillat","sequence":"additional","affiliation":[{"name":"Department of Biomedical Science, University of Lausanne, 1015 Lausanne, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fr\u00e9d\u00e9rique","family":"Ino","sequence":"additional","affiliation":[{"name":"Department of Biomedical Science, University of Lausanne, 1015 Lausanne, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gilles","family":"Aeschlimann","sequence":"additional","affiliation":[{"name":"Department of Biomedical Science, University of Lausanne, 1015 Lausanne, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xavier","family":"Ehret","sequence":"additional","affiliation":[{"name":"Department of Biomedical Science, University of Lausanne, 1015 Lausanne, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Ancin Del Olmo","sequence":"additional","affiliation":[{"name":"Department of Biomedical Science, University of Lausanne, 1015 Lausanne, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ver\u00f3nica","family":"Ponce de Le\u00f3n","sequence":"additional","affiliation":[{"name":"Department of Biomedical Science, University of Lausanne, 1015 Lausanne, Switzerland"},{"name":"National Center of Competence in Research Kidney.CH, 8057 Z\u00fcrich, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ute I.","family":"Scholl","sequence":"additional","affiliation":[{"name":"Department of Nephrology, School of Medicine, Heinrich-Heine-Universit\u00e4t D\u00fcsseldorf, 40225 D\u00fcsseldorf, Germany"},{"name":"Center of Functional Genomics, Berlin Institute of Health at Charit\u00e9, Universit\u00e4tsmedizin Berlin, 10117 Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Denise V.","family":"Winter","sequence":"additional","affiliation":[{"name":"National Center of Competence in Research Kidney.CH, 8057 Z\u00fcrich, Switzerland"},{"name":"Division of Molecular and Systems Toxicology, Department of Pharmaceutical Sciences, University of Basel, 4056 Basel, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6820-2712","authenticated-orcid":false,"given":"Alex","family":"Odermatt","sequence":"additional","affiliation":[{"name":"National Center of Competence in Research Kidney.CH, 8057 Z\u00fcrich, Switzerland"},{"name":"Division of Molecular and Systems Toxicology, Department of Pharmaceutical Sciences, University of Basel, 4056 Basel, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Edith","family":"Hummler","sequence":"additional","affiliation":[{"name":"Department of Biomedical Science, University of Lausanne, 1015 Lausanne, Switzerland"},{"name":"National Center of Competence in Research Kidney.CH, 8057 Z\u00fcrich, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2297-2738","authenticated-orcid":false,"given":"Sophia N.","family":"Verouti","sequence":"additional","affiliation":[{"name":"Department of Biomedical Science, University of Lausanne, 1015 Lausanne, Switzerland"},{"name":"National Center of Competence in Research Kidney.CH, 8057 Z\u00fcrich, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1007\/s11906-004-0046-0","article-title":"Glucocorticoid excess and hypertension","volume":"6","author":"Baid","year":"2004","journal-title":"Curr. 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