{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T04:01:47Z","timestamp":1782792107148,"version":"3.54.5"},"reference-count":49,"publisher":"Portland Press Ltd.","issue":"24","license":[{"start":{"date-parts":[[2021,12,6]],"date-time":"2021-12-06T00:00:00Z","timestamp":1638748800000},"content-version":"vor","delay-in-days":5,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2021,12,22]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Uromodulin (UMOD) is the most abundant renal protein secreted into urine by the thick ascending limb (TAL) epithelial cells of the loop of Henle. Genetic studies have demonstrated an association between UMOD risk variants and hypertension. We aimed to dissect the role of dietary salt in renal UMOD excretion in normotension and chronic hypertension. Normotensive Wistar\u2013Kyoto rats (WKY) and stroke-prone spontaneously hypertensive rats (SHRSP) (n=8\/sex\/strain) were maintained on 1% NaCl for 3 weeks. A subset of salt-loaded SHRSP was treated with nifedipine. Salt-loading in SHRSP increased blood pressure (\u0394SBP 35 \u00b1 5 mmHg, P&amp;lt;0.0001) and kidney injury markers such as kidney injury marker-1 (KIM-1; fold change, FC 3.4; P=0.003), neutrophil gelatinase-associated lipocalin (NGAL; FC, 2.0; P=0.012) and proteinuria. After salt-loading there was a reduction in urinary UMOD excretion in WKY and SHRSP by 26 and 55% respectively, compared with baseline. Nifedipine treatment reduced blood pressure (BP) in SHRSP, however, did not prevent salt-induced reduction in urinary UMOD excretion. In all experiments, changes in urinary UMOD excretion were dissociated from kidney UMOD protein and mRNA levels. Colocalization and ex-vivo studies showed that salt-loading increased intracellular UMOD retention in both WKY and SHRSP. Our study provides novel insights into the interplay among salt, UMOD, and BP. The role of UMOD as a cardiovascular risk marker deserves mechanistic reappraisal and further investigations based on our findings.<\/jats:p>","DOI":"10.1042\/cs20211017","type":"journal-article","created":{"date-parts":[[2021,12,6]],"date-time":"2021-12-06T14:16:57Z","timestamp":1638800217000},"page":"2749-2761","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Salt loading decreases urinary excretion and increases intracellular accumulation of uromodulin in stroke-prone spontaneously hypertensive rats"],"prefix":"10.1042","volume":"135","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9392-3020","authenticated-orcid":false,"given":"Sheon","family":"Mary","sequence":"first","affiliation":[{"name":"Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, Scotland, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philipp","family":"Boder","sequence":"additional","affiliation":[{"name":"Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, Scotland, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9023-0835","authenticated-orcid":false,"given":"Giacomo","family":"Rossitto","sequence":"additional","affiliation":[{"name":"Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, Scotland, U.K."},{"name":"Department of Medicine, University of Padua, Padua, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lesley","family":"Graham","sequence":"additional","affiliation":[{"name":"Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, Scotland, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kayley","family":"Scott","sequence":"additional","affiliation":[{"name":"Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, Scotland, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arun","family":"Flynn","sequence":"additional","affiliation":[{"name":"Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, Scotland, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Kipgen","sequence":"additional","affiliation":[{"name":"Department of Pathology, Queen Elizabeth University Hospital, Glasgow, Scotland, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Delyth","family":"Graham","sequence":"additional","affiliation":[{"name":"Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, Scotland, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2238-2612","authenticated-orcid":false,"given":"Christian","family":"Delles","sequence":"additional","affiliation":[{"name":"Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, Scotland, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2021,12,17]]},"reference":[{"key":"2021121710512835900_B1","doi-asserted-by":"publisher","first-page":"e1001177","DOI":"10.1371\/journal.pgen.1001177","article-title":"Genome-wide association study of blood pressure extremes identifies variant near UMOD associated with hypertension","volume":"6","author":"Padmanabhan","year":"2010","journal-title":"PLoS Genet."},{"key":"2021121710512835900_B2","doi-asserted-by":"publisher","first-page":"337","DOI":"10.1681\/ASN.2009070725","article-title":"Uromodulin levels associate with a common UMOD variant and risk for incident CKD","volume":"21","author":"Kottgen","year":"2010","journal-title":"J. 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