ENALAPRIL IMPROVES HEART-FAILURE INDUCED BY MONOCROTALINE WITHOUT REDUCING PULMONARY-HYPERTENSION IN RATS - ROLES OF PRESERVED MYOCARDIAL CREATINE-KINASE AND LACTATE-DEHYDROGENASE ISOENZYMES

We investigated the redistribution of myocardial isoenzymes of creatin e kinase (CK) and lactate dehydrogenase (LD) in rats with right heart failure induced by monocrotaline and assessed the effect of enalapril, an angiotensin converting enzyme inhibitor. Wistar rats were divided into four groups: (1) control (n = 20), (2) control + enalapril (25 mg /kg/day) (n = 22), (3) monocrotaline (50 mg/kg) (n = 45), (4) monocrot aline (50 mg/kg) + enalapril (25 mg/kg/day) (n = 32). After 4 weeks, t he monacrotaline group developed severe pulmonary hypertension and rig ht ventricular hypertrophy with marked decrease in myocardial norepine phrine and increase in both plasma atrial natriuretic peptide and mort ality rate (33.3%). The marked decrease in both MM and mitochondrial C K ('creatine shuttle') and the relatively constant BE and MB CK caused the net depression of total CK. The depression of LDI (aerobic LD) wa s remarkable compared with the relatively constant total LD. In the mo nocrotaline + enalapril group, mortality rate (9.4%), cardiac hypertro phy and plasma atrial natriuretic peptide were all significantly reduc ed and myocardial norepinephrine recovered although pulmonary hyperten sion was not improved at all. However, myocardial total, MM and mitoch ondrial CK and LD1 activities were all recovered completely or partial ly in this group. Thus, enalapril reduced cardiac hypertrophy and fail ure and improved the prognosis in this model of pulmonary hypertension . This beneficial effect of enalapril was not associated with pulmonar y vasodepression but with the inhibition of myocardial isoenzyme redis tribution of CK and LD, i.e. the preservation of 'creatine shuttle' an d aerobic LD.