{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,19]],"date-time":"2025-10-19T05:33:35Z","timestamp":1760852015053},"reference-count":22,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2009,1,30]],"date-time":"2009-01-30T00:00:00Z","timestamp":1233273600000},"content-version":"vor","delay-in-days":2009,"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":[[2003,8]]},"abstract":"<jats:p>\n<jats:list list-type=\"explicit-label\">\n<jats:list-item>\n<jats:p>Loop and thiazide diuretics are common therapeutic agents for the treatment of sodium retention and oedema. However, resistance to diuretics and decreases in renal function can develop during diuretic therapy. Adenosine causes renal vasoconstriction, sodium reabsorption, and participates in the tubuloglomerular feedback mechanism for the regulation of glomerular filtration rate.<\/jats:p>\n<\/jats:list-item>\n<jats:list-item>\n<jats:p>We tested the hypothesis that the selective adenosine A<jats:sub>1<\/jats:sub> receptor antagonist FK838 is orally active and causes diuresis and natriuresis, but maintains glomerular filtration rate in normal rats or in rats with furosemide resistance.<\/jats:p>\n<\/jats:list-item>\n<jats:list-item>\n<jats:p>In normal male Sprague \u2013 Dawley rats, FK838 dose\u2010dependently increased urine flow and sodium and chloride excretion while sparing potassium. In combination with furosemide, FK838 enhanced the diuretic and natriuretic actions of furosemide to the same extent as hydrochlorothiazide and did not increase the potassium loss in normal rats. In furosemide\u2010resistant rats, FK838 increased urine flow and electrolyte excretion to a greater extent than hydrochlorothiazide. In addition, hydrochlorothiazide significantly decreased glomerular filtration rate, whereas FK838 maintained glomerular filtration rate in furosemide\u2010resistant rats.<\/jats:p>\n<\/jats:list-item>\n<jats:list-item>\n<jats:p>This study shows that the adenosine A<jats:sub>1<\/jats:sub> receptor antagonist FK838 is orally active and causes potent diuresis and natriuresis and maintains glomerular filtration rate in normal or furosemide\u2010resistant rats. Adenosine A<jats:sub>1<\/jats:sub> receptor antagonists may be novel therapeutics for the treatment of oedema in normal or otherwise diuretic\u2010resistant patients.<\/jats:p>\n<\/jats:list-item>\n<\/jats:list>\n<\/jats:p><jats:p><jats:italic>British Journal of Pharmacology<\/jats:italic> (2003) <jats:bold>139<\/jats:bold>, 1383\u20131388. doi:<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1038\/sj.bjp.0705370\">10.1038\/sj.bjp.0705370<\/jats:ext-link><\/jats:p>","DOI":"10.1038\/sj.bjp.0705370","type":"journal-article","created":{"date-parts":[[2003,8,15]],"date-time":"2003-08-15T15:44:23Z","timestamp":1060962263000},"page":"1383-1388","update-policy":"http:\/\/dx.doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["An orally active adenosine A<sub>1<\/sub> receptor antagonist, FK838, increases renal excretion and maintains glomerular filtration rate in furosemide\u2010resistant rats"],"prefix":"10.1111","volume":"139","author":[{"given":"Christine G","family":"Schnackenberg","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emily","family":"Merz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David P","family":"Brooks","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2009,1,30]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.eurheartj.a014805"},{"key":"e_1_2_7_3_1","first-page":"1191","article-title":"CVT\u2010124, a novel adenosine A1 receptor antagonist with unique diuretic activity","volume":"286","author":"GELLAI M.","year":"1998","journal-title":"J. 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