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: Mingqiang Fu, Jingmin Zhou, Jianfeng Xu, Hongmin Zhu, Jianquan Liao, Xiaotong Cui, Aijun Sun, Michael Fu, Yunzeng Zou, Kai Hu, Junbo Ge
• Journal: Journal of cardiovascular pharmacology (J Cardiovasc Pharmacol) Vol. 63 Issue 3 Pg. 218-26 (Mar 2014) ISSN: 1533-4023 [Electronic] United States
• PMID: 24603116 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Angiotensin II Type 1 Receptor Blockers
• Imidazoles
• NFATC Transcription Factors
• Tetrazoles
• olmesartan
• Calcineurin

Topics

• Angiotensin II Type 1 Receptor Blockers (pharmacology)
• Animals
• Blood Pressure (drug effects)
• Calcineurin (genetics, metabolism)
• Cardiomegaly (drug therapy, pathology)
• Diastole
• Down-Regulation (drug effects)
• Fibrosis
• Heart Rate (drug effects)
• Hypertension (drug therapy, physiopathology)
• Imidazoles (pharmacology)
• Male
• NFATC Transcription Factors (genetics)
• Rats
• Rats, Inbred SHR
• Rats, Inbred WKY
• Tetrazoles (pharmacology)