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 creatine 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) monocrotaline (50 mg/kg) + enalapril (25 mg/kg/day) (n = 32). After 4 weeks, the monocrotaline group developed severe pulmonary hypertension and right ventricular hypertrophy with marked decrease in myocardial norepinephrine and increase in both plasma atrial natriuretic peptide and mortality rate (33.3%). The marked decrease in both MM and mitochondrial CK ('creatine shuttle') and the relatively constant BB and MB CK caused the net depression of total CK. The depression of LD1 (aerobic LD) was remarkable compared with the relatively constant total LD. In the monocrotaline+enalapril group, mortality rate (9.4%), cardiac hypertrophy and plasma atrial natriuretic peptide were all significantly reduced and myocardial norepinephrine recovered although pulmonary hypertension was not improved at all. However, myocardial total, MM and mitochondrial CK and LD1 activities were all recovered completely or partially in this group. Thus, enalapril reduced cardiac hypertrophy and failure and improved the prognosis in this model of pulmonary hypertension. This beneficial effect of enalapril was not associated with pulmonary vasodepression but with the inhibition of myocardial isoenzyme redistribution of CK and LD, i.e. the preservation of 'creatine shuttle' and aerobic LD.
Ishikawa
K
K
Second Department of Internal Medicine, Nagoya University School of Medicine, Japan.
Hashimoto
H
H
Mitani
S
S
Toki
Y
Y
Okumura
K
K
Ito
T
T
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000097:blood; D002312:Cardiomyopathy, Hypertrophic / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D003402:Creatine Kinase / Q000378:metabolism; D004656:Enalapril / Q000008:administration & dosage / Q000627:therapeutic use*; D006321:Heart / Q000187:drug effects*; D006976:Hypertension, Pulmonary / Q000139:chemically induced / Q000188:drug therapy*; D007527:Isoenzymes; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D016686:Monocrotaline; D009206:Myocardium / Q000201:enzymology; D009638:Norepinephrine / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D007527:Isoenzymes; D004656:Enalapril; D016686:Monocrotaline; D009320:Atrial Natriuretic Factor; D007770:L-Lactate Dehydrogenase; D003402:Creatine Kinase; D009638:Norepinephrine