Effect of losartan and benzbromarone on the level of human urate transporter 1 mRNA

Abstract

Both an angiotensin II receptor blocker, losartan (CAS 124750-99-8) and a serum urate lowering agent, benzbromarone (CAS 3562-84-3) exert a uricosuric action by inhibiting urate transporter 1 (URAT1). A recent clinical trial indicated that losartan could reduce the level of serum urate in hypertensive patients treated with urate lowering agents, suggesting the different mode of action of losartan from benzbromarone. In the present study, the effect of losartan and benzbromarone on the level of URAT1 mRNA was determined in transfected HEK293 cells. Losartan caused a significant reduction of its mRNA level, whereas it was not affected by benzbromarone. These results indicate that losartan decreases the level of human URAT1 mRNA, which may underlie the uricosuric action of losartan in hypertensive patients treated with serum urate lowering agents.

Impact of irbesartan, an angiotensin receptor blocker, on uric acid level and oxidative stress in high-risk hypertension patients

“…[24][25][26] The proximal tubule has been identified as the primary location for UA secretion and reabsorption. URAT1 has been shown to have a central role in proximal tubular UA reabsorption.…”

URAT1 Gene Polymorphisms Influence Uricosuric Action of Losartan in Hypertensive Patients with Hyperuricemia

“…Most previous studies focused on reducing blood pressure of lorsatan, but few studies investigated its uricosuric action. URAT1 was involved in the metabolism of serum uric acid and losartan could decrease SUA via inhibiting URAT1 transporter and decreasing the level of its mRNA [12,15,19,20]. The uricosuric efficacy of losartan presents individual differences in patients.…”

“…Owing to the specific benefit on urate metabolism, losartan has been known to ameliorate diuretic-induced hyperuricemia [6,7]. The mechanism of its special effect has been reported to result from the influence of mRNA level of urate transporter 1(URAT1) gene to inhibit the urate/anion transport in brush-border cells of the renal proximal tubules [8][9][10][11][12].…”

Total saponins from Discorea nipponica makino ameliorate urate excretion in hyperuricemic rats

“…[ 33 ] Benzbromarone was chosen as the positive drug because it could promote the excretion of uric acid. [ 34 ]…”

“…At present, drugs that are used for promoting the excretion of uric acid are mainly Probenecid, Sulfinpyrazone, and Benzbromarone. [ 33 34 ] They function mainly by inhibiting near-end kidney tubule from absorbing uric acid. Few of the patients will suffer from erythra, fever, and other side effects.…”