{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,24]],"date-time":"2026-01-24T23:57:00Z","timestamp":1769299020482,"version":"3.49.0"},"reference-count":44,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2017,3,23]],"date-time":"2017-03-23T00:00:00Z","timestamp":1490227200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001665","name":"Agence Nationale de la Recherche","doi-asserted-by":"publisher","award":["ANR\u201012\u2010BSV1\u20100031\u201001"],"award-info":[{"award-number":["ANR\u201012\u2010BSV1\u20100031\u201001"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001711","name":"Schweizerischer Nationalfonds zur F\u00f6rderung der Wissenschaftlichen Forschung","doi-asserted-by":"publisher","award":["P2LAP3_151782"],"award-info":[{"award-number":["P2LAP3_151782"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001711","name":"Schweizerischer Nationalfonds zur F\u00f6rderung der Wissenschaftlichen Forschung","doi-asserted-by":"publisher","award":["P300P3_158521"],"award-info":[{"award-number":["P300P3_158521"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2017,4,15]]},"abstract":"<jats:sec><jats:title>Key points<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>Hypercalcaemia can occur under various pathological conditions, such as primary hyperparathyroidism, malignancy or granulomatosis, and it induces natriuresis and polyuria in various species via an unknown mechanism.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>A previous study demonstrated that hypercalcaemia induced by vitamin D in rats increased endothelin (ET)\u20101 expression in the distal nephron, which suggests the involvement of the ET system in hypercalcaemia\u2010induced effects.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>In the present study, we demonstrate that, during vitamin D\u2010induced hypercalcaemia, the activation of ET system by increased ET\u20101 is responsible for natriuresis but not for polyuria.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Vitamin D\u2010treated hypercalcaemic mice showed a blunted response to amiloride, suggesting that epithelial sodium channel function is inhibited.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>We have identified an original pathway that specifically mediates the effects of vitamin D\u2010induced hypercalcaemia on sodium handling in the distal nephron without affecting water handling.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec><jats:sec><jats:title>Abstract<\/jats:title><jats:p>Acute hypercalcaemia increases urinary sodium and water excretion; however, the underlying molecular mechanism remains unclear. Because vitamin D\u2010induced hypercalcaemia increases the renal expression of endothelin (ET)\u20101, we hypothesized that ET\u20101 mediates the effects of hypercalcaemia on renal sodium and water handling. Hypercalcaemia was induced in 8\u2010week\u2010old, parathyroid hormone\u2010supplemented, male mice by oral administration of dihydrotachysterol (DHT) for 3\u00a0days. DHT\u2010treated mice became hypercalcaemic and displayed increased urinary water and sodium excretion compared to controls. mRNA levels of ET\u20101 and the transcription factors CCAAT\u2010enhancer binding protein \u03b2 and \u03b4 were specifically increased in the distal convoluted tubule and downstream segments in DHT\u2010treated mice. To examine the role of the ET system in hypercalcaemia\u2010induced natriuresis and polyuria, mice were treated with the ET\u20101 receptor antagonist macitentan, with or without DHT. Mice treated with both macitentan and DHT displayed hypercalcaemia and polyuria similar to that in mice treated with DHT alone; however, no increase in urinary sodium excretion was observed. To identify the affected sodium transport mechanism, we assessed the response to various diuretics in control and DHT\u2010treated hypercalcaemic mice. Amiloride, an inhibitor of the epithelial sodium channel (ENaC), increased sodium excretion to a lesser extent in DHT\u2010treated mice compared to control mice. Mice treated with either macitentan+DHT or macitentan alone had a similar response to amiloride. In summary, vitamin D\u2010induced hypercalcaemia increases the renal production of ET\u20101 and decreases ENaC activity, which is probably responsible for the rise in urinary sodium excretion but not for polyuria.<\/jats:p><\/jats:sec>","DOI":"10.1113\/jp273610","type":"journal-article","created":{"date-parts":[[2017,1,25]],"date-time":"2017-01-25T02:52:55Z","timestamp":1485312775000},"page":"2535-2550","source":"Crossref","is-referenced-by-count":7,"title":["Endothelin\u20101 mediates natriuresis but not polyuria during vitamin D\u2010induced acute hypercalcaemia"],"prefix":"10.1113","volume":"595","author":[{"given":"Natsuko","family":"Tokonami","sequence":"first","affiliation":[{"name":"Sorbonne Universit\u00e9, UPMC Univ Paris 06, INSERM, Universit\u00e9 Paris Descartes, Sorbonne Paris Cit\u00e9, UMR_S 1138 team 3 Centre de Recherche des Cordeliers  CNRS ERL 8228 Paris 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