Comparative Effects of Perindopril with Enalapril in Rats with Dilated Cardiomyopathy

Angiotensin-converting enzyme inhibitors have been shown to reduce morbidity and mortality in patients with heart failure. The angiotensin type-1 blocking and cardioprotective properties of perindopril and enalapril were studied in a rat model of dilated cardiomyopathy after autoimmune myocarditis. Enalapril at 20 mg/kg showed the same angiotensin type-1 blocking action as perindopril at 2 mg/kg in rats with heart failure. Twenty-eight days after immunization, surviving Lewis rats (90/120 = 75%) were divided into six groups and administered perindopril at 0.02, 0.2 and 2 mg/kg per day (Groups P0.02, P0.2 and P2), enalapril at 2 and 20 mg/kg per day (Groups E2 and E20) or vehicle alone (Group V, all groups n = 15). After oral administration for 1 month, four of 15 (27%) rats in Group V, and two (13%) in Groups P0.02 and E2 died. None of the animals in Groups P0.2, P2 and E20, or normal rats (Group N) died. Although both angiotensin-converting enzyme inhibitors improved ventricular function in a dose-dependent manner, the left ventricular end-diastolic pressure and area of myocardial fibrosis were lower, and ± dP/dt was higher in Group P2 (4.9 ± 0.6 mmHg, 7.5 ± 1.4% and +2651 ± 254/-2622 ± 189 mmHg/s, respectively) than in Group V (16.7 ± 1.3, 36 ± 2.6 and +2659 ± 176/-2516 ± 205, respectively) and Group E20 (7.5 ± 2.5, 15.6 ± 2.0 and +2018 ± 110/-2097 ± 102, respectively). Although the expression levels of transforming growth factor-β₁ and collagen-III mRNA in Group V (36.3 ± 5.7 and 157.6 ± 12.7%) were significantly higher than those in Group N (19.6 ± 3.0 and 65.2 ± 1.5%, both p < 0.01), they were reduced in Group P2 (21.4 ± 5.9 and 75.2 ± 9.3%, both p < 0.01). These results suggest that although enalapril can block increases in blood pressure caused by circulating angiotensin type-1, perindopril at 2 mg/kg may confer greater protection than enalapril at 20 mg/kg against injury from the renin-angiotensin system in heart failure.