{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,26]],"date-time":"2025-10-26T22:46:20Z","timestamp":1761518780166},"reference-count":30,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2009,2,3]],"date-time":"2009-02-03T00:00:00Z","timestamp":1233619200000},"content-version":"vor","delay-in-days":4020,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[1998,2]]},"abstract":"<jats:p>\n<jats:list list-type=\"explicit-label\">\n<jats:list-item><jats:p>The mechanism underlying the antidiuretic effect of thiazide diuretics in diabetes insipidus (DI) is unknown. This study addressed two specific questions: is the reduction in urine flow rate (<jats:italic>V<\/jats:italic>) related to a decrease in the delivery of fluid from the pars recta of the proximal tubules (\u2018distal delivery\u2019), and are there any changes in the expression and\/or intracellular distribution of vasopressin stimulated water channels (AQP2) in the collecting ducts, during chronic thiazide\u2010induced antidiuresis?<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Nine Brattleboro rats with vasopressin\u2010deficient DI were treated for 5 days with bendroflumethiazide (BFTZ), 9\u2003mg\u2003kg<jats:sup>\u22121<\/jats:sup> day<jats:sup>\u22121<\/jats:sup> orally, and 9 Brattleboro rats were left untreated. BFTZ\u2010treated DI rats showed a fall in <jats:italic>V<\/jats:italic> from \u223c200 to \u223c75\u2003ml day<jats:sup>\u22121<\/jats:sup> and an increase in urine osmolality from \u223c130 to \u223c400\u2003mosmol\u2003kg<jats:sup>\u22121<\/jats:sup>.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>BFTZ\u2010induced antidiuresis was associated with a persistent loss of sodium, but not of potassium. After 5 days of treatment, clearance studies in conscious rats showed a tendency towards decreases in effective renal plasma flow (\u22127%), GFR (\u221212%) and lithium clearance (<jats:italic>C<\/jats:italic><jats:sub>Li<\/jats:sub>; used as marker for distal delivery) (\u221225%), compared with untreated controls, but none of these changes were statistically significant. There was no apparent relationship between <jats:italic>C<\/jats:italic><jats:sub>Li<\/jats:sub> and <jats:italic>V<\/jats:italic> in BFTZ\u2010treated or untreated DI rats.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>BFTZ treatment did not change the expression of AQP2 in homogenates of cortex, outer or inner medulla from DI rats, or from normal Long Evans rats. Light and electron microscopic immunocyto\u2010chemistry revealed no changes in intracellular distribution of AQP2 in principal cells from inner medullary collecting ducts of BFTZ\u2010treated DI rats.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>We concluded, (i) that although the antidiuretic effect of BFTZ in rats with DI is associated with a net loss of Na, the decrease in <jats:italic>V<\/jats:italic> shows no association with changes in distal delivery, as estimated by <jats:italic>C<\/jats:italic><jats:sub>Li<\/jats:sub>. (ii) Antidiuretic treatment with BFTZ does not alter the expression of subcellular distribution of AQP2 water channels in the collecting ducts. The mechanism underlying the chronic antidiuresis caused by thiazide diuretics in DI remains elusive.<\/jats:p><\/jats:list-item>\n<\/jats:list>\n<\/jats:p><jats:p><jats:italic>British Journal of Pharmacology<\/jats:italic> (1998) <jats:bold>123<\/jats:bold>, 737\u2013745; doi:<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1038\/sj.bjp.0701653\">10.1038\/sj.bjp.0701653<\/jats:ext-link><\/jats:p>","DOI":"10.1038\/sj.bjp.0701653","type":"journal-article","created":{"date-parts":[[2005,1,28]],"date-time":"2005-01-28T19:19:06Z","timestamp":1106939946000},"page":"737-745","update-policy":"http:\/\/dx.doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Mechanism of antidiuresis caused by bendroflumethiazide in conscious rats with diabetes insipidus"],"prefix":"10.1111","volume":"123","author":[{"given":"Lene","family":"Gr\u00f8nbeck","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Marples","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S\u00f8ren","family":"Nielsen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sten","family":"Christensen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2009,2,3]]},"reference":[{"key":"e_1_2_6_2_1","first-page":"319","article-title":"Effect of hydrochlorothiazide on renal electrolyte gradient in glucose diuresis and experimental diabetes insipidus","volume":"137","author":"Baer J.E.","year":"1962","journal-title":"J. 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