Effects of combination of irbesartan and perindopril on calcineurin expression and sarcoplasmic reticulum Ca2+-ATPase activity in rat cardiac pressure-overload hypertrophy
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Aim: To observe effects of angiotensin (Ang) II receptor antagonist (AT1) irbesartan and angiotensin-converting enzyme (ACE) inhibitor perindopril on rat myocardium calcineurin expression and sarcoplasmic reticulum Ca2+-ATPase activity in the model of pressure-overload cardiac hypertrophy. Methods: Forty male adult Sprague Dawley rats were divided into 5 groups. One group was treated by sham operation; four groups were myocardium hypertrophy cases caused by banding aortic above renal artery. Drugs were given one week after operation. Group 1: sham group, rats (n=8) were gavaged with normal saline 2 ml/(kg·d) (ig); Group 2: control group, rats (n=8) were treated with normal saline 2 ml/(kg·d) (ig); Group 3: rats (n=8) were given perindopril 2 mg/(kg·d) (ig); Group 4: rats (n=8) were treated with irbesartan 20 mg/(kg·d) (ig); Group 5: rats (n=8) were given irbesartan 20 mg/(kg·d) plus perindopril 2 mg/(kg·d) (ig). Morphometric determination, calcineurin expression and sarcoplasmic reticulum Ca2+-ATPase activity were done at the end of 6 week of drug intervention. Expression of calcineurin in myocardium was detected by immunohistochemistry. Results: Left ventricular mass index (LVMI), transverse diameter of myocardial cell (TDM), calcineurin activity were remarkably decreased after drug intervention and this decrease was most remarkable in the combination drug therapy group. Sarcoplasmic reticulum Ca2+-ATPase activity was increased after drug intervention, especially in the combined drug therapy group. Calcineurin expression in myocardium was remarkably decreased after drug intervention. LVMI was positively correlated with TDM and calcineurin, negatively correlated with sarcoplasmic reticulum Ca2+-ATPase. Conclusion: These data suggest that irbesartan and perindopril inhibit cardiac hypertrophy through the increased activity of sarcoplasmic reticulum Ca2+-ATPase and decreased expression of calcineurin. Their combination had better effects on regressing of ventricular hypertrophy.
Key wordsAngiotensin (Ang) II receptor antagonist Angiotensin-converting enzyme inhibitor Calcineurin Sarcoplasmic reticulum Ca2+-ATPase Pressure overload Cardiac hypertrophy Rat
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- Grossman, W., Jones, D., McLaurin, L.P., 1975. Wall stress and patterns of hypertrophy in the human left ventricle. J. Clin. Invest., 55:56–64.Google Scholar
- Sadoshima, J., Izumo, S., 1997. The cellular and molecular response of cardiac myocytes to mechanical stress. Ann. Rev. Physiol., 59(1):551–571. [doi:10.1146/annurev.physiol.59.1.551]Google Scholar
- Sussman, M.A., Lim, H.W., Gude, N., Taigen, T., Olson, E.N., Robbins, J., Colbert, M.C., Gualberto, A., Wieczorek, D.F., Molkentin, J.D., 1998. Prevention of cardiac hypertrophy in mice by calcineurin inhibition. Science, 281(5383):1690–1693. [doi:10.1126/science.281.5383.1690]CrossRefPubMedGoogle Scholar
- Zhang, W., Kowal, R.C., Rusnak, F., 2000. Failure of calcineurin inhibitors to prevent pressure-overload left ventricular hypertrophy in rats. Circ. Res., 84(6):722–728.Google Scholar