title: Losartan alleviates hyperuricemia-induced atherosclerosis in a rabbit model.
abstract: OBJECTIVE
  To investigate the mechanisms underlying the therapeutic effects of losartan on hyperuricemia-induced aortic atherosclerosis, in an experimental rabbit model.
  
  
  METHODS
  Male rabbits (n = 48) were divided into control, hyperuricemia (HU), hypercholesterolemia + hyperuricemia (HC + HU) and high-purine with 30-mg/kg/d losartan (HU + losartan) groups. Serum uric acid (UA) and plasma renin and angiotensin II activities were determined. Aortic tissue specimens were analyzed for histological changes and proliferating cell nuclear antigen (PCNA). Liver tissues were sampled for quantitative analyses of liver low-density lipoprotein receptor (LDLR) mRNA and protein via reverse transcription polymerase chain reaction and western blotting.
  
  
  RESULTS
  After 12 weeks, serum UA and plasma renin and plasma angiotensin II activities were enhanced in the HU and HU + HC groups (P < 0.001) compared to the control, whereas in the HU + losartan group plasma renin activity was not different and serum UA concentrations as well as plasma angiotensin II activity were moderately enhanced (P < 0.05). Smooth muscle cell (SMC) PCNA expression increased strongly in the HU and HU + HC groups (P < 0.001), but was less pronounced in the HU + losartan group. In contrast, transcription and expression of LDLR mRNA and protein were significantly higher in the control and HU + losartan groups compared to the HU and HU + HC groups. Both the HU and HU + HC groups had elevated intima thickness and intima areas compared to the control and HU + losartan groups.
  
  
  CONCLUSIONS
  Losartan can alleviate experimental atherosclerosis induced by hyperuricemia.
authors.affiliation: Department of Cardiology, Xuhui District Central Hospital Shanghai, China.
authors.forename: Hongchao
authors.initials: H
authors.lastname: Zheng
authors.affiliation: Department of Cardiology, Xuhui District Central Hospital Shanghai, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Li
authors.affiliation: Department of Cardiology, Xuhui District Central Hospital Shanghai, China.
authors.forename: Yueyou
authors.initials: Y
authors.lastname: Ding
authors.affiliation: Department of Cardiology, Xuhui District Central Hospital Shanghai, China.
authors.forename: Peizhi
authors.initials: P
authors.lastname: Miao
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001011:Aorta / Q000187:drug effects / Q000473:pathology; D050197:Atherosclerosis / Q000209:etiology / Q000473:pathology*; D015153:Blotting, Western; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000187:drug effects; D033461:Hyperuricemia / Q000150:complications*; D007150:Immunohistochemistry; D008077:Lipoproteins, LDL; D019808:Losartan / Q000494:pharmacology*; D008297:Male; D046529:Microscopy, Electron, Transmission; D011817:Rabbits; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014527:Uric Acid / Q000097:blood / Q000378:metabolism
chemical_list: D000959:Antihypertensive Agents; D008077:Lipoproteins, LDL; D014527:Uric Acid; D019808:Losartan
keywords: Atherosclerosis; hyperuricemia; losartan; proliferating cell nuclear antigen; vascular smooth muscle cell