Comparative effects of angiotensin II receptor blockade (candesartan) with angiotensin-converting enzyme inhibitor (quinapril) in rats with dilated cardiomyopathy

Angiotensin II receptor blockers and angiotensin-converting enzyme inhibitors have been shown to reduce morbidity and mortality in patients with heart failure, but their inhibitory actions on angiotensin I-induced increases in blood pressure in heart failure are not clear. Angiotensin I blocking and cardioprotective properties of the angiotensin II receptor blocker candesartan and the angiotensin-converting enzyme inhibitor quinapril were studied in a rat model of dilated cardiomyopathy after autoimmune myocarditis. Low-dose candesartan (0.5 mg/kg) showed the same angiotensin I blocking action as high-dose quinapril (20 mg/kg) in rats with heart failure. Twenty-eight days after immunization, surviving Lewis rats (43/58, 74%) were divided into three groups and given quinapril at 20 mg/kg per day (group Q, n = 14), candesartan at 0.5 mg/kg per day (group C, n = 14) or vehicle alone (group V, n = 15). After oral administration for 1 month, four of 15 (27%) rats in group V and two of 14 (14%) in group C died. None of the animals in group Q died. Although angiotensin II levels of the blood and the left ventricle in group V [367 ± 26 and 437 ± 18% versus normal rats (group N)] were significantly higher than those in group N (both p < 0.01), they were reduced in group Q (88 ± 32 and 169 ± 53%, both p < 0.01). The left ventricular end-diastolic pressure and the area of myocardial fibrosis were lower, and the first derivative ±dP/dt was higher in group Q (7.0 ± 1.7 mmHg, 9 ± 3% and +3451 ± 170/-3182 ± 186 mmHg/s, respectively) than in group V (16.7 ± 1.3 mmHg, 36 ± 6% and +2601 ± 235/-2156 ± 257 mmHg/s, respectively) and in group C (11.2 ± 2.0 mmHg, 26 ± 4% and +3063 ± 164/-2734 ± 174 mmHg/s, respectively). Although levels of expression of transforming growth factor β1 and collagen III mRNA in group V (367 ± 26 and 437 ± 18% versus group N) were significantly higher than those in group N (both p < 0.01), they were reduced in group Q (88 ± 32 and 169 ± 53%, both p < 0.01). These results suggested that although low-dose candesartan can block increases in blood pressure with circulating angiotensin I to the same extent as high-dose quinapril, it does not confer sufficient protection against injury from the renin-angiotensin system in heart failure.