Inhibition of progression of heart failure and expression of TGF-β1 mRNA in rats with heart failure by the ace inhibitor quinapril

The cardioprotective effects of quinapril, an angiotensin-converting enzyme inhibitor, were studied in a rat model of heart failure. Twenty-six rats were divided into two groups: one given 20 mg/kg/day quinapril (n = 11), and controls given 0.5% methylcellulose (n = 15). After oral administration for 1 month, quinapril reduced heart weight (from 1.28 ± 0.05 to 0.87 ± 0.02 g; p < 0.05) without changing body weight. Quinapril lowered left ventricular end-diastolic pressure (from 14.1 ± 2.0 to 6.6 ± 1.5 mmHg; p < 0.05) and central venous pressure (from 2.7 ± 0.9 to 0.7 ± 0.4 mmHg), and increased ± dP/dt (from +2409 ± 50 to +3569 ± 169 mmHg/s, and from -2318 ± 235 to -3960 ± 203 mmHg/s; both p < 0.01). The area of myocardial fibrosis was markedly reduced by quinapril (6 ± 3%) as compared with controls (29 ± 6%; p < 0.01). Expression of transforming growth factor (TGF)-β1 mRNA was markedly increased in controls as compared with age-matched normal rats. The increase in level of TGF-β1 mRNA was significantly suppressed by quinapril (from 17.1 ± 6.2 to 9.00 ± 2.40; p < 0.05). These observations indicated that quinapril has cardioprotective effects on heart failure, and that the beneficial effects may be partly explained by attenuation of fibrotic response through suppression of TGF-β1 mRNA expression.