title: Olmesartan attenuates cardiac hypertrophy and improves cardiac diastolic function in spontaneously hypertensive rats through inhibition of calcineurin pathway.
abstract: OBJECTIVE
  To test whether olmesartan ameliorates cardiac diastolic dysfunction in spontaneously hypertensive rats (SHRs) through calcineurin pathway.
  
  
  METHODS
  Twenty-four male SHRs of 6 months were divided into saline- (n = 12) and olmesartan-treated (n = 12) groups. Age-matched WKY (n = 12) rats served as controls. Saline (10 mL·kg·d) or the same volume of olmesartan liquor (2.5 mg·kg·d) was administered by gavage for 3 months. Heart rate, systolic blood pressure, cardiac structure, and function and histological studies were determined. Expression of calcineurin and downstream NFAT3 were also detected.
  
  
  RESULTS
  Compared with age-matched Wistar Kyoto rats, SHRs of 6 months exhibited evident cardiac hypertrophy and diastolic dysfunction as demonstrated by elevated systolic blood pressure and E/E', decreased E/A and E'/A', while F, left ventricular ejection fraction and fractional shortening remained unimpaired. Treatment with olmesartan significantly decreased systolic blood pressure and ventricular hypertrophy, attenuated fibrosis, and improved diastolic function (all P < 0.05). Meanwhile, both calcineurin and NFAT3 expressions were downregulated in olmesartan group compared with the other 2 groups (both P < 0.05).
  
  
  CONCLUSIONS
  These data suggest the beneficial effect of olmesartan on cardiac structure and diastolic dysfunction, and it may be mediated through calcineurin pathway. This indicates a new therapeutic target for diastolic dysfunction.
authors.affiliation: *Department of Cardiology, Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai, China; †Department of Medicine, Sahlgrenska University Hospital/Sahlgrenska, Gothenburg, Sweden; and ‡Institutes of Biomedical Sciences, Fudan University, Shanghai, China.
authors.forename: Mingqiang
authors.initials: M
authors.lastname: Fu
authors.forename: Jingmin
authors.initials: J
authors.lastname: Zhou
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Xu
authors.forename: Hongmin
authors.initials: H
authors.lastname: Zhu
authors.forename: Jianquan
authors.initials: J
authors.lastname: Liao
authors.forename: Xiaotong
authors.initials: X
authors.lastname: Cui
authors.forename: Aijun
authors.initials: A
authors.lastname: Sun
authors.forename: Michael
authors.initials: M
authors.lastname: Fu
authors.forename: Yunzeng
authors.initials: Y
authors.lastname: Zou
authors.forename: Kai
authors.initials: K
authors.lastname: Hu
authors.forename: Junbo
authors.initials: J
authors.lastname: Ge
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D019703:Calcineurin / Q000235:genetics / Q000378:metabolism*; D006332:Cardiomegaly / Q000188:drug therapy* / Q000473:pathology; D003971:Diastole; D015536:Down-Regulation / Q000187:drug effects; D005355:Fibrosis; D006339:Heart Rate / Q000187:drug effects; D006973:Hypertension / Q000188:drug therapy / Q000503:physiopathology; D007093:Imidazoles / Q000494:pharmacology*; D008297:Male; D050778:NFATC Transcription Factors / Q000235:genetics; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013777:Tetrazoles / Q000494:pharmacology*
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D007093:Imidazoles; D050778:NFATC Transcription Factors; D013777:Tetrazoles; C437965:olmesartan; D019703:Calcineurin