Effects of angiotensin converting enzyme inhibitor, angiotensin II type I receptor blocker and their combination on postinfarcted ventricular remodeling in rats / 中华医学杂志(英文版)

ABSTRACT

<p><b>BACKGROUND</b>Transforming growth factor (TGF) beta(1)-Smads signal plays an important role in cardiac remodeling following myocardial infarction (MI). In addition, both angiotensin converting enzyme inhibitor (ACEI) and angiotensin II type I receptor blocker (ARB) can effectively prevent left ventricular remodeling. The current study focused on whether the combination of ACEI and ARB is more beneficial for preventing ventricular remodeling and whether Smad proteins mediate this beneficial effect.</p><p><b>METHODS</b>MI was induced by ligating the left anterior descending coronary artery in rats. Twenty-four hours after ligation, the survived rats were randomly divided into five groups and treated for 8 weeks placebo group, ACEI group (benazepril 10 mg.kg(-1).d(-1)), ARB group (irbesartan 50 mg.kg(-1).d(-1)), ACEI + ARB group (benazepril 10 mg.kg(-1).d(-1) + irbesartan 50 mg.kg(-1).d(-1)) and control group (sham-operated rats). After 8 weeks, we examined the following indexes the ratio of ventricular weight to body weight (VW/BW), left ventricular end diastolic dimension (LVDd), ejection fraction (EF), fractional shortening (FS), ratio of E-wave to A-wave velocity, collagen of noninfarcted zone, the mRNA expression of TGFbeta(1), Smad 2, and Smad 3 by RT-PCR in noninfarcted zone, the protein expression of Smad 2 and Smad 3 in noninfarcted zone by Western blot.</p><p><b>RESULTS</b>VW/BW significantly increased in the placebo groups compared with that in the control group (P < 0.01). This increase was limited in ACEI, ARB, and combined groups (P < 0.01 compared with placebo group). There was no significant difference among the three actively treated groups. Collagen was increased in placebo group (5.68 +/- 0.5)% compared with that in control group (P < 0.01). ACEI, ARB and combined treatment attenuated this increase of collagen [(4.3 +/- 0.5)%, (3.5 +/- 0.5)%, (3.2 +/- 0.4)%] in comparison with that in placebo group (P < 0.01 respectively). Combined treatment showed more significant effect on collagen deposition. EF and FS significantly decreased, LVDd and E/A significantly increased in placebo group compared with that in control group (P < 0.01 respectively). ACEI, ARB and combined treatment ameliorated these indexes (P < 0.01 compared with placebo group). The mRNA expression of TGFbeta(1), Smad 2, and Smad 3 (0.700 +/- 0.045, 0.959 +/- 0.037 and 0.850 +/- 0.051) increased in placebo group compared with that in control group (P < 0.01). ACEI, ARB and combined treatment normalized the increase (P < 0.01). Furthermore, ARB and combined treatment proved to be more effective in decreasing TGF beta(1) and Smad mRNA expression than ACEI treatment (P < 0.01). The expression of Smad 2 and Smad 3 protein increased in placebo group compared with that in control group (P < 0.01). ACEI, ARB and combined treatment normalized the increase (P < 0.01). Furthermore, ARB and combined treatment proved to be more effective than ACEI alone (P < 0.01).</p><p><b>CONCLUSIONS</b>TGFbeta(1)-Smads signal activation is correlated with ventricular remodeling following MI. ACEI and ARB treatment prevents ventricular remodeling by inhibiting expression of Smad 2 and Smad 3. ARB and combined treatment are more effective than ACEI alone.</p>