title: Effects of fosinopril and losartan on renal Klotho expression and oxidative stress in spontaneously hypertensive rats.
abstract: OBJECTIVE
  To explore effects of fosinopril and losartan on renal Klotho expression and oxidative stress in spontaneously hypertensive rats (SHR) and the mechanisms underlying the protection against renal damage.
  
  
  METHODS
  Fifteen male SHRs (22 weeks old) were randomly divided into 3 groups (n=5 in each group): a SHR group, a fosinopril group [10 mg/(kg.d)], and a losartan group [50 mg/(kg.d)]. Age-matched Wistar-Kyoto (WKY) rats were chosen for a control group. Eight weeks later, tail arterial pressure, 24 hours urinary protein (Upro),urinary N-acetyl-β-D-glucosaminidase (NAGase) were measured. Renal pathological changes were examined under light microscopy by HE staining. The renal mRNA and protein expression of Klotho were determined by RT-PCR, immunohistochemical staining or Western blot. The levels of total antioxidant capacity (TAOC), malondialdehyde (MDA), Cu/Zn superoxide dismutase (Cu/Zn-SOD), Mn superoxide dismutase (Mn-SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) were determined.
  
  
  RESULTS
  The typical pathological characteristics of hypertensive renal damage were observed in the kidney of the SHR group.Compared with the SHR group, the systolic pressure, Upro, and urinary NAGase, the content of MDA and renal pathological damage was reduced while the renal Klotho expression and activities of TAOC, Cu/Zn-SOD, CAT, and GSH-Px were increased (P<0.05 or P<0.01) in the fosinopril or losartan group. There was no significant difference in renal Mn-SOD level among the 4 groups (P>0.05).
  
  
  CONCLUSIONS
  Fosinopril and losartan can exert protection against hypertensive renal damage through upregulating Klotho expression as well as reducing oxidative stress.
authors.affiliation: Department of Nephrology, Xiangya Hospital, Central South University, Changsha 410008, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Tang
authors.forename: Qiaoling
authors.initials: Q
authors.lastname: Zhou
authors.forename: Zhichun
authors.initials: Z
authors.lastname: Liu
authors.forename: Zhou
authors.initials: Z
authors.lastname: Xiao
authors.forename: Veeraragoo
authors.initials: V
authors.lastname: Pouranan
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D017328:Fosinopril / Q000494:pharmacology*; D005966:Glucuronidase / Q000235:genetics / Q000378:metabolism*; D006973:Hypertension / Q000235:genetics* / Q000473:pathology; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D000090265:Klotho Proteins; D019808:Losartan / Q000494:pharmacology*; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY
chemical_list: D000959:Antihypertensive Agents; D012333:RNA, Messenger; D005966:Glucuronidase; D000090265:Klotho Proteins; D019808:Losartan; D017328:Fosinopril