title: Uricosuric action of losartan via the inhibition of urate transporter 1 (URAT 1) in hypertensive patients.
abstract: BACKGROUND
  The angiotensin receptor blocker losartan inhibited urate transporter 1 (URAT1) according to in vitro experiments. However, it is still unknown whether the inhibitory effect of losartan on URAT1 contributes to its uricosuric action in humans.
  
  
  METHODS
  Thirty-two patients with hypertension and nine patients with idiopathic renal hypouricemia (five with and four without hypertension) were enrolled for this study. Hypertensive patients were prescribed oral losartan (50 mg/day, n = 16) or candesartan (8 mg/day, n = 16). Before and after 1-month treatment, the serum concentration of urate (Sur) and creatinine (Scr), and the clearance value of urate (Cur) and creatinine (Ccr) were determined. Clearance studies using the URAT1 inhibitor benzbromarone (100 mg/day) or losartan (50 mg/day) loading test were also performed in these patients.
  
  
  RESULTS
  Blood pressure (BP) significantly decreased in the patients treated with either losartan or candesartan. Losartan significantly reduced Sur, which was associated with a concomitant increase in the Cur/Ccr ratio, whereas candesartan did not alter these parameters. In hypertensive patients with loss-of-function mutation of URAT1, losartan did not alter either Sur or Cur/Ccr, nor did benzbromarone. The lack of effect of URAT1 inhibitors on renal excretion of urate was independent of the renal function of hypouricemic patients. On the other hand, both losartan and benzbromarone increased Cur/Ccr ratio in hypertensive patients harboring the wild URAT1 gene, regardless of the presence of hypouricemia.
  
  
  CONCLUSIONS
  These findings suggested that losartan inhibited URAT1 and thereby it lowered Sur levels in hypertensive patients.
authors.affiliation: Department of Cardiovascular Medicine, Faculty of Medicine, Tottori University, Yonago, Japan. thammer@chukai.ne.jp
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Hamada
authors.forename: Kimiyoshi
authors.initials: K
authors.lastname: Ichida
authors.forename: Makoto
authors.initials: M
authors.lastname: Hosoyamada
authors.forename: Einosuke
authors.initials: E
authors.lastname: Mizuta
authors.forename: Kiyotaka
authors.initials: K
authors.lastname: Yanagihara
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Sonoyama
authors.forename: Shinobu
authors.initials: S
authors.lastname: Sugihara
authors.forename: Osamu
authors.initials: O
authors.lastname: Igawa
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Hosoya
authors.forename: Akira
authors.initials: A
authors.lastname: Ohtahara
authors.forename: Chiaki
authors.initials: C
authors.lastname: Shigamasa
authors.forename: Yasutaka
authors.initials: Y
authors.lastname: Yamamoto
authors.forename: Haruaki
authors.initials: H
authors.lastname: Ninomiya
authors.forename: Ichiro
authors.initials: I
authors.lastname: Hisatome
mesh_terms: D000284:Administration, Oral; D000368:Aged; D047228:Angiotensin II Type 1 Receptor Blockers / Q000008:administration & dosage / Q000627:therapeutic use*; D001562:Benzimidazoles / Q000008:administration & dosage; D001713:Biphenyl Compounds; D001794:Blood Pressure / Q000502:physiology; D004247:DNA / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D033461:Hyperuricemia / Q000209:etiology / Q000235:genetics / Q000378:metabolism*; D019808:Losartan / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D009154:Mutation; D027361:Organic Anion Transporters / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D027701:Organic Cation Transport Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D016133:Polymerase Chain Reaction; D013777:Tetrazoles / Q000008:administration & dosage; D016896:Treatment Outcome; D014527:Uric Acid / Q000378:metabolism
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D027361:Organic Anion Transporters; D027701:Organic Cation Transport Proteins; C491241:SLC22A12 protein, human; D013777:Tetrazoles; D014527:Uric Acid; D004247:DNA; D019808:Losartan; C081643:candesartan