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J Cardiovasc Pharmacol. 2014 Mar;63(3):218-26. doi: 10.1097/FJC.0000000000000038.

Olmesartan attenuates cardiac hypertrophy and improves cardiac diastolic function in spontaneously hypertensive rats through inhibition of calcineurin pathway.

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  • 1*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.

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.

PMID:
24603116
[PubMed - in process]
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