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. 2006 Mar;7(3):228-34.
doi: 10.1631/jzus.2006.B0228.

Effects of combination of irbesartan and perindopril on calcineurin expression and sarcoplasmic reticulum Ca2+-ATPase activity in rat cardiac pressure-overload hypertrophy

Qing-jun Jiang  1 , Geng Xu, Fei-fei Mao, You-fa Zhu
Affiliations

Effects of combination of irbesartan and perindopril on calcineurin expression and sarcoplasmic reticulum Ca2+-ATPase activity in rat cardiac pressure-overload hypertrophy

Qing-jun Jiang et al. J Zhejiang Univ Sci B. 2006 Mar.

Abstract

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 Ca(2+)-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 Ca(2+)-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 Ca(2+)-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 Ca(2+)-ATPase.

Conclusion: These data suggest that irbesartan and perindopril inhibit cardiac hypertrophy through the increased activity of sarcoplasmic reticulum Ca(2+)-ATPase and decreased expression of calcineurin. Their combination had better effects on regressing of ventricular hypertrophy.

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Figures

Fig. 1
Fig. 1
Expression of calcineurin in rat myocardium detected by immunohistochemistry. Semi-quantitative analysis showed that the calcineurin expression in control group was larger than that of irbesartan group, perindopril group and combination group (P<0.01) Cont: Control; Peri: Perindopril; Irbe: Irbesartan; Comb: Combination; **P<0.01, vs control group
Fig. 2
Fig. 2
Calcineurin (CaN) activity of cardiac myocardium. Calcineurin activity in control group as larger than that of irbesartan group, perindopril group and combination group (P<0.05) Cont: Control; Peri: Perindopril; Irbe: Irbesartan; Comb: Combination; *P<0.05, vs control group; ΔP<0.05, vs sham group
Fig. 3
Fig. 3
Sarcoplasmic reticulum (SR) Ca2+-ATPase activity of rat cardiac myocardium. The sarcoplasmic reticulum Ca2+-ATPase activity of normal cardiac myocardium in the sham group was very high. Sarcoplasmic reticulum Ca2+-ATPase activity in the control group was lower than that of perindopril group, irbesartan group, and combination group Cont: Control; Peri: Perindopril; Irbe: Irbesartan; Comb: Combination; * P<0.05, vs control group; ΔP<0.05, vs sham group; §P<0.05, vs combination group
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