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


CONCLUSIONS
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.
Jiang
Qing-jun
QJ
Department of Cardiology, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, China.
Xu
Geng
G
Mao
Fei-fei
FF
Zhu
You-fa
YF
D000818:Animals; D001713:Biphenyl Compounds / Q000008:administration & dosage*; D019703:Calcineurin / Q000378:metabolism*; D000252:Calcium-Transporting ATPases / Q000378:metabolism*; D006332:Cardiomegaly / Q000209:etiology / Q000378:metabolism*; D004195:Disease Models, Animal; D004338:Drug Combinations; D006321:Heart / Q000187:drug effects; D006973:Hypertension / Q000150:complications / Q000378:metabolism*; D000077405:Irbesartan; D008297:Male; D009206:Myocardium / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism; D020913:Perindopril / Q000008:administration & dosage*; D011312:Pressure; D051381:Rats; D017207:Rats, Sprague-Dawley; D012519:Sarcoplasmic Reticulum / Q000187:drug effects / Q000201:enzymology*; D013777:Tetrazoles / Q000008:administration & dosage*
D001713:Biphenyl Compounds; D004338:Drug Combinations; D013777:Tetrazoles; D019703:Calcineurin; D000252:Calcium-Transporting ATPases; D000077405:Irbesartan; D020913:Perindopril