Abstract

To explore the effect of the angiotensin type 1 (AT-1) receptor antagonist, Irbesartan, on myocardial interstitial fibrosis in rats with diabetic cardiomyopathy (DCM). Thirty-nine male wistar rats were injected intraperitoneally with streptozotocin (STZ) (55 mg/kg, once) to establish a DCM animal model. After 12 weeks, the rats with blood glucose higher than 16.7 mmol/L, as well as polydipsia、hyperphagia and polyuria, were randomly divided into three groups: control, Irbesartan and A779+Irbesartan group. Rats in control were infused normal saline, in Irbesartan were infused Irbesartan (50 mg/kg) and in A779+Irbesartan were infused Irbesartan and were injected with A779 (100 ng/kg) once daily. At the end of the experiment, left ventricular internal dimension systole (LVIDs)、left ventricular internal dimension diastole (LVIDd)、E/A、left ventricular ejection fraction (LVEF)、shortening fraction (FS) were measured. Then collagen content and the messenger ribonucleic acid (mRNA) expression of angiotensin-convertion enzyme 2 (ACE2) were detected. At the end of the experiment, the LVIDs, LVIDd and the collagen content of Irbesartan and A779+Irbesartan were significantly lower than control (P<0.01), E/A, FS, LVEF and the expression of ACE2 mRNA of Irbesartan and A779+Irbesartan were higher than control (P<0.01). The LVIDs, LVIDd and collagen content of A779+Irbesartan were higher than Irbesartan (P<0.05), E/A, FS, LVEF of A779+Irbesartan were lower than Irbesartan (P<0.05). However, there was no significant difference in the expression of ACE2 mRNA between Irbesartan and A779+Irbesartan. Irbesartan amelioorates myocardial interstitial fibrosis via angiotensin-(1-7) (Ang-(1-7))

Key words: Irbesartan, angiotensin-(1-7), angiotensin-convertion enzyme-2, A779, diabetes mellitus, cardiomyopathy.

Abbreviation

ACE2, Angiotensin-converting enzyme 2; Ang-(1-7), angiotensin-(1-7); Ang II,     angiotensin II; AT-1, angiotensin type 1; DCM, diabetic cardiomyopathy; FS, shortening fraction; LVEF, left ventricular ejection fraction; LVIDd, left ventricular internal dimension diastole; LVIDs, left ventricular internal dimension systole; RAS, rennin–angiotensin system;SD, standard deviation; STZ, streptozotocin; mRNA, messenger ribonucleic acid; MAPK, mitogen-activated protein kinase; cDNA, completmentary deoxyribonucleic acid; RT-PCR, reverse transcriptase-polymerase chain reaction.