{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T20:46:28Z","timestamp":1778273188591,"version":"3.51.4"},"reference-count":31,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2017,12,29]],"date-time":"2017-12-29T00:00:00Z","timestamp":1514505600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100008392","name":"Sundhed og Sygdom, Det Frie Forskningsr\u00e5d","doi-asserted-by":"publisher","award":["FSS 6110\u201000131B"],"award-info":[{"award-number":["FSS 6110\u201000131B"]}],"id":[{"id":"10.13039\/100008392","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Acta Physiologica"],"published-print":{"date-parts":[[2018,5]]},"abstract":"Abstract<\/jats:title>Aim<\/jats:title>The \u201cvoltage hypothesis\u201d of H+<\/jats:sup> secretion states that urinary acidification following increased Na+<\/jats:sup> delivery to the collecting duct (CD<\/jats:styled-content>) is EN<\/jats:styled-content>aC dependent leading to transepithelial voltage\u2010dependent increase in H+<\/jats:sup> secretion. We recently showed that furosemide acidifies the urine independently of EN<\/jats:styled-content>aC activity. If the voltage hypothesis holds, hydrochlorothiazide (HCT<\/jats:styled-content>) must acidify the urine. We here tested the acute effect of HCT<\/jats:styled-content> on urine pH<\/jats:styled-content> under normal and high EN<\/jats:styled-content>aC expression.<\/jats:p><\/jats:sec>Methods<\/jats:title>Mice subjected to a control or a low\u2010Na+<\/jats:sup> diet were anesthetized and infused (0.5 mL h\u22121<\/jats:sup>) with saline. Catheterization of the urinary bladder allowed real\u2010time measurement of diuresis and urine pH<\/jats:styled-content>. Mice received either HCT<\/jats:styled-content> (1 mg mL\u22121<\/jats:sup>) or vehicle. Urinary Na+<\/jats:sup> and K+<\/jats:sup> excretions were determined by flame photometry. EN<\/jats:styled-content>aC expression levels were measured by semi\u2010quantitative Western blotting.<\/jats:p><\/jats:sec>Results<\/jats:title>(1) HCT<\/jats:styled-content> increased diuresis and natriuresis in both diet groups. (2) K+<\/jats:sup> excretion rates increased after HCT<\/jats:styled-content> administration from 18.6 \u00b1 1.3 to 31.7 \u00b1 2.5 \u03bcmol h\u22121<\/jats:sup> in the control diet group and from 23.0 \u00b1 1.3 to 48.7 \u00b1 3.0 \u03bcmol h\u22121<\/jats:sup> in the low\u2010Na+<\/jats:sup> diet group. (3) Mice fed a low\u2010Na+<\/jats:sup> diet showed a marked upregulation of EN<\/jats:styled-content>aC. (4) Importantly, no acute changes in urine pH<\/jats:styled-content> were observed after the administration of HCT<\/jats:styled-content> in either group.<\/jats:p><\/jats:sec>Conclusion<\/jats:title>Acute administration of HCT<\/jats:styled-content> has no effect on urine pH<\/jats:styled-content>. Similarly, substantial functional and molecular upregulation of EN<\/jats:styled-content>aC did not cause HCT<\/jats:styled-content> to acutely change urine pH<\/jats:styled-content>. Thus, an increased Na+<\/jats:sup> load to the CD<\/jats:styled-content> does not alter urine pH<\/jats:styled-content>. This supports our previous finding and likely falsifies the voltage hypothesis of H+<\/jats:sup> secretion.<\/jats:p><\/jats:sec>","DOI":"10.1111\/apha.13013","type":"journal-article","created":{"date-parts":[[2017,12,11]],"date-time":"2017-12-11T07:32:59Z","timestamp":1512977579000},"source":"Crossref","is-referenced-by-count":6,"title":["Hydrochlorothiazide and acute urinary acidification: The \u201cvoltage hypothesis\u201d of ENaC\u2010dependent H+<\/sup> secretion refuted"],"prefix":"10.1111","volume":"223","author":[{"given":"N.","family":"Ayasse","sequence":"first","affiliation":[{"name":"Department of Biomedicine, Physiology and Biophysics Aarhus University Aarhus C Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P. I. 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