Effects of Angiotensin II Receptor Blockers on Renal Handling of Uric Acid in Rats

• LI Yan

  Tokyo University of Science, Faculty of Pharmaceutical Sciences

• SATO Masanobu

  Tokyo University of Science, Faculty of Pharmaceutical Sciences Faculty of Parmacy, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University

• YANAGISAWA Yuichi

  Tokyo University of Science, Faculty of Pharmaceutical Sciences

• MAMADA Hideaki

  Tokyo University of Science, Faculty of Pharmaceutical Sciences Faculty of Parmacy, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University

• FUKUSHI Akimasa

  Tokyo University of Science, Faculty of Pharmaceutical Sciences Faculty of Parmacy, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University

• MIKAMI Kentaro

  Tokyo University of Science, Faculty of Pharmaceutical Sciences

• SHIRASAKA Yoshiyuki

  Tokyo University of Science, Faculty of Pharmaceutical Sciences Faculty of Parmacy, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University

• TAMAI Ikumi

  Tokyo University of Science, Faculty of Pharmaceutical Sciences Faculty of Parmacy, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University

Bibliographic Information

Other Title

• Effects of angiotensin II receptor blockers on renal handling of urate in rats

Abstract

  Elevated serum uric acid level has been associated with increased cardiovascular risk in hypertensive patients. Several angiotensin II receptor blockers exhibit differential effects on regulation of serum uric acid level in humans. We have demonstrated that some angiotensin II receptor blockers trans-stimulate the uptake of uric acid by human URAT1 and others inhibit the transport of uric acid mediated by human URAT1, OAT1, OAT3 and MRP4 in vitro. This study investigated the effects of candesartan, pratosartan and telmisartan on renal handling of uric acid in rats in vivo and in vitro. Candesartan (0.1 mg/kg) significantly decreased the urinary excretion of uric acid and increased the plasma uric acid concentration. The kidney candesartan level after low-dose treatment is close to that required to trans-stimulate uric acid uptake in vitro. Pratosartan exhibited dose-dependent hypouricemic and uricosuric effects, while telmisartan showed no effects on plasma uric acid level. Furthermore, we confirmed the effects of the tested drugs on uric acid transport by rat renal brush border membrane transporter(s) and basolateral Oat1 and Oat3. Effects of angiotensin II receptor blockers in rats may be mainly determined by their intrinsic effects (cis-inhibition and trans-stimulation) on uric acid reabsorption transporter(s) and their pharmacokinetic properties in rats.<br>

Journal

• Drug Metabolism and Pharmacokinetics

  Drug Metabolism and Pharmacokinetics 23 (4), 263-270, 2008

  The Japanese Society for the Study of Xenobiotics

Keywords

• Angiotensin II Receptor Blockers
• Uric Acid
• Rat
• Transporter

Details

• CRID: 1390282680157787392
• NII Article ID: 10021956330
• NII Book ID: AA1162652X
• DOI: 10.2133/dmpk.23.263
• COI: 1:CAS:528:DC%2BD1cXht12itLrN
• ISSN: 18800920
• ISSN: 13474367
• Web Site: http://api.elsevier.com/content/article/PII:S1347436715301956?httpAccept=text/xml
• Web Site: http://api.elsevier.com/content/article/PII:S1347436715301956?httpAccept=text/plain
• Web Site: https://search.jamas.or.jp/link/ui/2009059457
• Text Lang: en
• Data Source:
  • JaLC
  • Crossref
  • CiNii Articles
• Abstract License Flag: Disallowed