LACK OF CORRELATION OF HYPOTENSIVE EFFECTS WITH PREVENTION OF CARDIAC-HYPERTROPHY BY PERINDOPRIL AFTER LIGATION OF RAT CORONARY-ARTERY

1 The present study was designed to test the hypothesis that beneficia l effects of angiotensin converting enzyme (ACE)inhibitors are indepen dent of a fall in blood pressure in rat experimental heart failure fol lowing coronary ligation. 2 The animals were assigned randomly to six groups; sham operation, controls subjected to coronary ligation (contr ol), coronary ligation plus chronic treatment with ACE inhibitors at n on- and hypotensive doses; perindopril (0.2 or 2 mg kg(-1) day(-1)) or enalapril (2 or 20 mg kg(-1) day(-1)) for three weeks starting one we ek after the ligation. 3 Systemic blood pressure was measured every we ek during the experiments. At the end of the treatments, cardiac funct ion and heart weight (an index of myocardial hypertrophy) were determi ned. In the other animals, ACE activities in plasma and tissues includ ing heart, kidney, lung and blood vessels were measured. 4 In the cont rols, cardiac ACE activity, weight of right ventricle and left ventric ular end-diastolic pressure (LVEDP) were higher compared to those in t he sham-operated animals four weeks after the coronary ligation. Howev er, ACE activities were not changed in plasma, kidney, lung and aorta by ligation of the coronary artery. 5 The chronic treatment with perin dopril at a dose of 0.2 mg kg(-1) day(-1) inhibited the increase in AC E activity in cardiac tissue and suppressed the right ventricular hype rtrophy without affecting systemic haemodynamics. In contrast, enalapr il at a dose of 20 mg kg(-1) day(-1), but not 2 mg kg(-1) day(-1), pre vented the development of the right ventricular hypertrophy. Enalapril at 20 mg kg(-1) day(-1) also lowered systemic blood pressure. 6 There is no significant correlation between systemic blood pressure and rig ht ventricular hypertrophy at the end of the treatment with perindopri l (r = 0.06) or enalapril (r = 0.1). 7 These findings demonstrate that perindopril, an ACE inhibitor, prevents cardiac hypertrophy without a ffecting systemic blood pressure in the rat with heart failure after c oronary ligation, and suggest that selective augmentation of ACE activ ity in cardiac tissue is involved in the progression of hypertrophy in this model.