title: Aliskiren reduced renal fibrosis in mice with chronic ischemic kidney injury--beyond the direct renin inhibition.
abstract: Chronic renal ischemia leads to renal fibrosis and atrophy. Activation of the renin-angiotensin-aldosterone system is one of the main mechanisms driving chronic renal ischemic injury. The aim of the present study was to define the effect of aliskiren in chronic ischemia of the kidney. Two-kidney, one-clip mice were used to study chronic renal ischemia. Aliskiren significantly lowered the blood pressure in mice with renal artery constriction (92.1±1.1 vs. 81.0±1.8 mm Hg, P<0.05). Renin expression was significantly increased in ischemic kidneys when treated with aliskiren. In addition, (Pro)renin receptor expression was decreased by aliskiren in ischemic kidneys. Aliskiren treatment significantly increased klotho expression and reduced the expression of fibrogenic cystokines, caspase-3 and Bax in ischemic kidneys. Histological examination revealed that aliskiren significantly reduced the nephrosclerosis score (4.5±1.9 vs. 7.3±0.4, P<0.05). Immunofluorescence staining also showed that aliskiren decreased the deposition of interstitial collagen I in ischemic kidneys. In conclusion, direct renin inhibition significantly reduced renal fibrosis and apoptosis following chronic renal ischemia.
authors.affiliation: School of Medicine, Chang Gung University, Taoyuan, Taiwan.
authors.forename: Chiao-Yin
authors.initials: CY
authors.lastname: Sun
authors.forename: Wen-Jin
authors.initials: WJ
authors.lastname: Cherng
authors.forename: Hui-Zhen
authors.initials: HZ
authors.lastname: Jian
authors.forename: Hsiang-Hao
authors.initials: HH
authors.lastname: Hsu
authors.forename: I-Wen
authors.initials: IW
authors.lastname: Wu
authors.forename: Heng-Jung
authors.initials: HJ
authors.lastname: Hsu
authors.forename: Mai-Szu
authors.initials: MS
authors.lastname: Wu
mesh_terms: D000577:Amides / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology / Q000627:therapeutic use; D053148:Caspase 3 / Q000378:metabolism; D024042:Collagen Type I / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D005355:Fibrosis; D005650:Fumarates / Q000494:pharmacology / Q000627:therapeutic use*; D005966:Glucuronidase / Q000378:metabolism; D007511:Ischemia / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D007668:Kidney / Q000098:blood supply* / Q000187:drug effects / Q000473:pathology*; D007676:Kidney Failure, Chronic / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D000090265:Klotho Proteins; D051379:Mice; D008815:Mice, Inbred Strains; D012077:Renal Artery / Q000503:physiopathology; D012083:Renin / Q000378:metabolism; D013525:Surgical Instruments; D000092502:Renin Inhibitors
chemical_list: D000577:Amides; D000959:Antihypertensive Agents; D053148:Caspase 3; D024042:Collagen Type I; D005650:Fumarates; D005966:Glucuronidase; D000090265:Klotho Proteins; D012083:Renin; D000092502:Renin Inhibitors; C446481:aliskiren