title: Fosinopril and losartan regulate klotho gene and nicotinamide adenine dinucleotide phosphate oxidase expression in kidneys of spontaneously hypertensive rats.
abstract: OBJECTIVE
  Klotho, a newly identified antiaging gene, predominantly detected in the kidney, has pleiotropic protective effects on kidney diseases. Several studies have confirmed the association between Klotho and oxidative stress. The present studies were performed to explore effects of fosinopril (Fos) and losartan (Los) on Klotho and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase expression in kidneys of spontaneously hypertensive rats (SHR).
  
  
  METHODS
  Twenty-four male 22-week-old SHR were randomly divided into three groups: model group, Fos group and Los group. Wistar-Kyoto rats were taken as control. After 8 weeks, urinary N-acetyl-β-D-glucosaminidase (NAGase), 24 h urinary protein (Upro), serum creatinine (Scr), blood urea nitrogen (BUN) and renal pathological changes were detected. Renal mRNA and protein expression of Klotho and three subunits of NADPH oxidase protein expression were evaluated.
  
  
  RESULTS
  As compared to the model group, NAGase, Upro, Scr and BUN were decreased; the typical renal pathological damage was relieved in the Fos or Los group. Fos or Los inhibited the reduction of Klotho expression, and reduced the elevation of NADPH oxidase expression.
  
  
  CONCLUSIONS
  Abnormal expression of Klotho and NADPH oxidase plays important roles in progression of hypertensive renal damage. Fos and Los can increase Klotho expression, and inhibit NADPH oxidase expression, which may be one of the mechanisms of their protective effects in hypertensive renal damage.
authors.affiliation: Department of Nephrology, Xiangya Hospital, Xiangya Medical College, Central South University, Changsha, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Tang
authors.forename: Qiao-Ling
authors.initials: QL
authors.lastname: Zhou
authors.forename: Xiang
authors.initials: X
authors.lastname: Ao
authors.forename: Wei-Sheng
authors.initials: WS
authors.lastname: Peng
authors.forename: Pouranan
authors.initials: P
authors.lastname: Veeraragoo
authors.forename: Tian-Feng
authors.initials: TF
authors.lastname: Tang
mesh_terms: D000818:Animals; D018450:Disease Progression; D017328:Fosinopril / Q000494:pharmacology* / Q000627:therapeutic use; D015971:Gene Expression Regulation, Enzymologic; D005966:Glucuronidase / Q000096:biosynthesis* / Q000235:genetics; D006973:Hypertension / Q000188:drug therapy / Q000201:enzymology* / Q000235:genetics; D007668:Kidney / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D000090265:Klotho Proteins; D019808:Losartan / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D019255:NADPH Oxidases / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D011897:Random Allocation; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY
chemical_list: D012333:RNA, Messenger; D019255:NADPH Oxidases; D005966:Glucuronidase; D000090265:Klotho Proteins; D019808:Losartan; D017328:Fosinopril