Key result
Dual irbesartan and perindopril markedly reduces left ventricular mass index and calcineurin activity in rats.
Why the study?
The effects of irbesartan and perindopril on calcineurin expression and sarcoplasmic reticulum Ca2+-ATPase activity in pressure-overload cardiac hypertrophy were not well characterized.
Answers are grounded in this paper and cite their sources.
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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Jiang et al. (2006) studied pressure-overload cardiac hypertrophy (n=40). Irbesartan and perindopril combination vs. Sham, normal saline control, perindopril alone, and irbesartan alone was evaluated on Left ventricular mass index (LVMI), transverse diameter of myocardial cell (TDM), calcineurin activity, and sarcoplasmic reticulum Ca(2+)-ATPase activity. The combination of irbesartan and perindopril remarkably decreased left ventricular mass index and calcineurin activity, and increased sarcoplasmic reticulum Ca(2+)-ATPase activity in rats.
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