{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T20:05:32Z","timestamp":1786133132073,"version":"build-2736575974"},"reference-count":0,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[1999,4]]},"abstract":"<jats:sec>\n                    <jats:title>Abstract.<\/jats:title>\n                    <jats:p>\n                      The natriuretic and diuretic action of a highly selective adenosine A\n                      <jats:sub>1<\/jats:sub>\n                      receptor (A\n                      <jats:sub>1<\/jats:sub>\n                      AdoR) antagonist, 1,3-dipropyl-8-[2-(5,6-epoxy)norbornyl]xanthine (CVT-124), was investigated in anesthetized rats. CVT-124 (0.1 to 1 mg\/kg) caused dose-dependent increases in urine flow and fractional and absolute sodium excretion of by six- to 10-fold and, at 0.1 mg\/kg, increased the GFR (1.6 \u00b1 0.1 to 2.5 \u00b1 0.2 ml\/min;\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt; 0.01). There were no changes in BP or heart rate. CVT-124 reduced absolute proximal reabsorption (26 \u00b1 3 to 20 \u00b1 2 nl\/min;\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt; 0.05) despite unchanged proximally measured, single-nephron GFR (SNGFR) (42 \u00b1 5 to 44 \u00b1 4 nl\/min; NS) and thereby decreased fractional proximal reabsorption (60 \u00b1 3 to 46 \u00b1 4%;\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt; 0.05). Despite increasing distal tubular fluid flow rate (5.4 \u00b1 0.7 to 9.7 \u00b1 0.9 nl\/min;\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt; 0.001), it reduced the proximal-distal difference in SNGFR (before: 9.4 \u00b1 1.0\n                      <jats:italic toggle=\"yes\">versus<\/jats:italic>\n                      during CVT-124: 4.6 \u00b1 1.5 nl\/min;\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt; 0.01), suggesting that it had blunted the effects of the macula densa on SNGFR. Direct measurements of maximal tubuloglomerular feedback (TGF) responses were made from proximal stop flow pressure (PSF) during orthograde loop perfusion from the proximal tubule with artificial tubular fluid at 40 nl\/min. TGF was blunted by intravenous CVT-124 (0.5 mg\/kg; \u25b5PSF with vehicle: 8.3 \u00b1 0.6\n                      <jats:italic toggle=\"yes\">versus<\/jats:italic>\n                      CVT-124: 6.5 \u00b1 0.3 mmHg;\n                      <jats:italic toggle=\"yes\">n<\/jats:italic>\n                      = 9;\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt; 0.01). In conclusion, A\n                      <jats:sub>1<\/jats:sub>\n                      AdoR blockade reduces proximal reabsorption and uncouples it from glomerular filtration. It increases distal delivery of fluid yet does not activate a macula densa-dependent fall in SNGFR because it blunts the TGF response. Natriuresis accompanied by blockade of proximal glomerulotubular balance and TGF characterizes a new class of diuretic drugs.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1681\/asn.v104714","type":"journal-article","created":{"date-parts":[[2021,4,28]],"date-time":"2021-04-28T04:35:36Z","timestamp":1619584536000},"page":"714-720","source":"Crossref","is-referenced-by-count":118,"title":["Natriuretic and Diuretic Actions of a Highly Selective Adenosine A1 Receptor Antagonist"],"prefix":"10.1681","volume":"10","author":[{"given":"CHRISTOPHER S.","family":"WILCOX","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"WILLIAM J.","family":"WELCH","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"GEORGE F.","family":"SCHREINER","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"LUIZ","family":"BELARDINELLI","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","container-title":["Journal of the American Society of Nephrology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ovid.com\/00001751-199904000-00004","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T19:29:09Z","timestamp":1786130949000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ovid.com\/00001751-199904000-00004"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1999,4]]},"references-count":0,"journal-issue":{"issue":"4","published-print":{"date-parts":[[1999]]}},"URL":"https:\/\/doi.org\/10.1681\/asn.v104714","relation":{},"ISSN":["1046-6673"],"issn-type":[{"value":"1046-6673","type":"print"}],"subject":[],"published":{"date-parts":[[1999,4]]}}}