Quinapril inhibits progression of heart failure and fibrosis in rats with dilated cardiomyopathy after myocarditis.
The cardioprotective properties of quinapril, an angiotensin-converting enzyme inhibitor, were studied in a rat model of dilated cardiomyopathy. Twenty-eight days after immunization of pig cardiac myosin, four groups rats were given 0.2 mg/kg (Q0.2, n = 11), 2 mg/kg (Q2, n = 11) or 20 mg/kg (Q20, n = 11) of quinapril or vehicle (V, n = 15) orally once a day. After 1 month, left ventricular end-diastolic pressure (LVEDP), +/- dP/dt, area of myocardial fibrosis, and myocardial mRNA expression of transforming growth factor (TGF)-beta1, collagen-III and fibronectin were measured. Four of 15 (27%) rats in V and two of 11 (18%) in Q0.2 died. None of the animals in Q2 or Q20 died. The LVEDP was higher and +/- dP/dt was lower in V (14.1 +/- 2.0 mmHg and +2409 +/- 150/-2318 +/- 235 mmHg/sec) than in age-matched normal rats (5.0 +/- 0.6 mmHg and +6173 +/- 191/-7120 +/- 74 mmHg/ sec; all p < 0.01). After quinapril treatment, LVEDP was decreased and +/- dP/dt was increased in a dose-dependent manner (10.8 +/- 1.8 mmHg and +3211 +/- 307/-2928 +/- 390 mmHg/sec in Q0.2, 9.4 +/- 1.5 mmHg and +2871 +/- 270/-2966 +/- 366 mmHg/sec in Q2, and 6.6 +/- 1.5 mmHg, and +3569 +/- 169/-3960 +/- 203 mmHg/sec in Q20). Increased expression levels of TGF-beta1, collagen-III and fibronectin mRNA in V were reduced in Q20. Quinapril improved survival rate and cardiac function in rats with dilated cardiomyopathy after myocarditis. Furthermore, myocardial fibrosis was regressed and myocardial structure returned to nearly normal in animals treated with quinapril.
Juan
Wen
W
Department of Clinical Pharmacology, Niigata University of Pharmacy and Applied Life Sciences, Niigata, Japan.
Nakazawa
Mikio
M
Watanabe
Kenichi
K
Ma
Meilei
M
Wahed
Mir I I
MI
Hasegawa
Go
G
Naito
Makoto
M
Yamamoto
Tadashi
T
Fuse
Koichi
K
Kato
Kiminori
K
Kodama
Makoto
M
Aizawa
Yoshifusa
Y
D000284:Administration, Oral; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002311:Cardiomyopathy, Dilated / Q000188:drug therapy* / Q000473:pathology* / Q000503:physiopathology; D024061:Collagen Type III / Q000032:analysis / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005353:Fibronectins / Q000032:analysis / Q000378:metabolism; D005355:Fibrosis / Q000188:drug therapy; D015870:Gene Expression; D006334:Heart Function Tests / Q000187:drug effects; D008297:Male; D009205:Myocarditis / Q000473:pathology*; D000077583:Quinapril; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D015996:Survival Rate; D044005:Tetrahydroisoquinolines / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000032:analysis / Q000378:metabolism; D053773:Transforming Growth Factor beta1; D016277:Ventricular Function, Left / Q000187:drug effects; D017725:Ventricular Pressure / Q000187:drug effects
D000806:Angiotensin-Converting Enzyme Inhibitors; D024061:Collagen Type III; D005353:Fibronectins; D012333:RNA, Messenger; D044005:Tetrahydroisoquinolines; C508962:Tgfb1 protein, rat; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D000077583:Quinapril