Document Detail


Effects of angiotensin II receptor blockers on renal handling of uric acid in rats.
MedLine Citation:
PMID:  18762713     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Yan Li; Masanobu Sato; Yuichi Yanagisawa; Hideaki Mamada; Akimasa Fukushi; Kentaro Mikami; Yoshiyuki Shirasaka; Ikumi Tamai
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Drug metabolism and pharmacokinetics     Volume:  23     ISSN:  1880-0920     ISO Abbreviation:  Drug Metab. Pharmacokinet.     Publication Date:  2008  
Date Detail:
Created Date:  2008-09-02     Completed Date:  2008-11-18     Revised Date:  2014-01-09    
Medline Journal Info:
Nlm Unique ID:  101164773     Medline TA:  Drug Metab Pharmacokinet     Country:  Japan    
Other Details:
Languages:  eng     Pagination:  263-70     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Absorption
Angiotensin II Type 1 Receptor Blockers / pharmacology*
Animals
Benzimidazoles / pharmacology
Benzoates / pharmacology
Imidazoles / pharmacology
Kidney / metabolism*
Male
Metabolic Clearance Rate
Rats
Rats, Sprague-Dawley
Tetrazoles / pharmacology
Urate Oxidase / metabolism
Uric Acid / metabolism*
Xanthine Oxidase / metabolism
Chemical
Reg. No./Substance:
0/Angiotensin II Type 1 Receptor Blockers; 0/Benzimidazoles; 0/Benzoates; 0/Imidazoles; 0/Tetrazoles; 268B43MJ25/Uric Acid; 66VLQ6E6DL/pratosartan; EC 1.17.3.2/Xanthine Oxidase; EC 1.7.3.3/Urate Oxidase; S8Q36MD2XX/candesartan; U5SYW473RQ/telmisartan

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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