Inhibition of progression of heart failure and expression of TGF-beta 1 mRNA in rats with heart failure by the ACE inhibitor quinapril.

Abstract

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.

• Authors: M Ma, K Watanabe, M I Wahed, M Inoue, T Sekiguchi, T Kouda, Y Ohta, M Nakazawa, Y Yoshida, T Yamamoto, H Hanawa, M Kodama, K Fuse, Y Aizawa
• Journal: Journal of cardiovascular pharmacology (J Cardiovasc Pharmacol) Vol. 38 Suppl 1 Pg. S51-4 (Oct 2001) ISSN: 0160-2446 [Print] United States
• PMID: 11811359 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Angiotensin-Converting Enzyme Inhibitors
• Isoquinolines
• RNA, Messenger
• Tetrahydroisoquinolines
• Tgfb1 protein, rat
• Transforming Growth Factor beta
• Transforming Growth Factor beta1
• Quinapril

Topics

• Administration, Oral
• Angiotensin-Converting Enzyme Inhibitors (pharmacology, therapeutic use)
• Animals
• Disease Progression
• Heart Failure (metabolism, mortality, prevention & control)
• Isoquinolines (pharmacology, therapeutic use)
• Male
• Myocarditis (metabolism, mortality, prevention & control)
• Quinapril
• RNA, Messenger (antagonists & inhibitors, biosynthesis)
• Rats
• Rats, Inbred Lew
• Tetrahydroisoquinolines
• Transforming Growth Factor beta (antagonists & inhibitors, biosynthesis, genetics)
• Transforming Growth Factor beta1