Inhibition of progression of heart failure and expression of TGF-beta 1 mRNA in rats with heart failure by the ACE inhibitor quinapril.
The cardioprotective effects of quinapril, an angiotensin-converting enzyme inhibitor, were studied in a rat model of heart failure. Twenty-six rats were divided into two groups: one given 20 mg/kg/day quinapril (n = 11), and controls given 0.5% methylcellulose (n = 15). After oral administration for 1 month, quinapril reduced heart weight (from 1.28+/-0.05 to 0.87+/-0.02 g; p < 0.05) without changing body weight. Quinapril lowered left ventricular end-diastolic pressure (from 14.1+/-2.0 to 6.6+/-1.5 mmHg; p < 0.05) and central venous pressure (from 2.7+/-0.9 to 0.7+/-0.4 mmHg), and increased +/- dP/dt (from +2409+/-50 to +3569+/-169 mmHg/s, and from -2318+/-235 to -3960+/-203 mmHg/s; both p < 0.01). The area of myocardial fibrosis was markedly reduced by quinapril (6+/-3%) as compared with controls (29+/-6%; p < 0.01). Expression of transforming growth factor (TGF)-beta1 mRNA was markedly increased in controls as compared with age-matched normal rats. The increase in level of TGF-beta1 mRNA was significantly suppressed by quinapril (from 17.1+/-6.2 to 9.00+/-2.40; p < 0.05). These observations indicated that quinapril has cardioprotective effects on heart failure, and that the beneficial effects may be partly explained by attenuation of fibrotic response through suppression of TGF-beta1 mRNA expression.
Ma
M
M
Department of Clinical Pharmacology, Niigata College of Pharmacy, Japan.
Watanabe
K
K
Wahed
M I
MI
Inoue
M
M
Sekiguchi
T
T
Kouda
T
T
Ohta
Y
Y
Nakazawa
M
M
Yoshida
Y
Y
Yamamoto
T
T
Hanawa
H
H
Kodama
M
M
Fuse
K
K
Aizawa
Y
Y
D000284:Administration, Oral; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D018450:Disease Progression; D006333:Heart Failure / Q000378:metabolism / Q000401:mortality / Q000517:prevention & control*; D007546:Isoquinolines / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D009205:Myocarditis / Q000378:metabolism / Q000401:mortality / Q000517:prevention & control; D000077583:Quinapril; D012333:RNA, Messenger / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D051381:Rats; D011917:Rats, Inbred Lew; D044005:Tetrahydroisoquinolines; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D053773:Transforming Growth Factor beta1
D000806:Angiotensin-Converting Enzyme Inhibitors; D007546:Isoquinolines; D012333:RNA, Messenger; D044005:Tetrahydroisoquinolines; C508962:Tgfb1 protein, rat; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D000077583:Quinapril