Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.15.1 (ACE)
 18,300 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The purpose of this study is to determine whether the administration of the ACE inhibitor cilazapril can lessen the adverse effects of ventricular remodeling, including systolic and diastolic dysfunction, modulation of fetal gene expression, increase of collagen genes, and depression of the sarcoplasmic reticulum (SR) Ca2+ ATPase gene in a myocardial infarcted (MI) rat model. At 1 day after MI, the animals were randomly assigned to cilazapril treatment or no treatment. We performed Doppler-echocardiographic examinations and measured cardiac mRNA in rats at 1 month and 3 months after MI (each group n = 8). The weights of the right (RV) and left ventricles (LV) in 1- and 3-month MI rats were significantly larger than those of the control rats. Cilazapril significantly prevented the increase. The MI rats showed systolic dysfunction, as evidenced by decreased fractional shortening (control, 34 +/- 3% vs. MI, 17 +/- 3%; P < 0.01) and ejection fraction measured by the modified Simpson's method (control, 61 +/- 2% vs. MI, 36 +/- 3%; P < 0.01) in rats at 1 month after operation. MI rats showed diastolic dysfunction, defined as increased peak early filling velocity, increased deceleration rate of the early filling wave, decreased late filling velocity, and an increase in the ratio of early filling to late filling velocity. Cilazapril significantly prevented systolic and diastolic dysfunction in rats after MI. The increases in beta-MHC, alpha-skeletal actin, ANP, and collagen I and III mRNAs in the nonischemic LV and RV were significantly suppressed by treatment with cilazapril. Depressed SR Ca(2+)-ATPase mRNA (nonischemic LV, 0.7-fold, P < 0.05 vs. control; RV, 0.5-fold, P < 0.05 vs. control) at 3 months after MI was significantly restored to normal levels by cilazapril. Cilazapril improved the adverse remodeling process by attenuating the progression of systolic and diastolic dysfunction, and prevented abnormal cardiac gene expression following MI.
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PMID:Effect of cilazapril on ventricular remodeling assessed by Doppler-echocardiographic assessment and cardiac gene expression. 960 33

Both systolic and diastolic cardiac dysfunction coexist in various degrees in the majority of patients with heart failure. Although ACE inhibitors are useful in the treatment of heart failure, the roles of bradykinin in the systolic and diastolic properties of left ventricular function under long-term treatment of ACE inhibitor have not been fully elucidated. We therefore evaluated the changes in left ventricular function, histomorphometry, and the expression of several failing heart related genes, by use of an orally active specific bradykinin type 2 receptor antagonist, FR173657 (0.3 mg/kg per day), with an ACE inhibitor, enalapril (1 mg/kg per day), in dogs with tachycardia-induced heart failure (270 ppm, 22 days) and compared the effects to enalapril alone. Although there were no differences observed in blood pressure, left ventricular dimension, and percentage of fractional shortening, FR173657 significantly increased left ventricular filling pressure (P<0.01), prolonged the time constant of relaxation (P<0.05), and suppressed the expression of endothelial NO synthase and sarcoplasmic reticulum Ca(2+)-ATPase mRNA (P<0.05). FR173657 also upregulated collagen type I and III mRNA (P<0.05) and increased the total amount of cardiac collagen deposits (P<0.05) in left ventricle compared with that in the enalapril-treated group. In conclusion, endogenous bradykinin contributes to the cardioprotective effect of ACE inhibitor, improving left ventricular diastolic dysfunction rather than systolic dysfunction, via modification of NO release and Ca(2+) handling and suppression of collagen accumulation.
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PMID:Bradykinin improves left ventricular diastolic function under long-term angiotensin-converting enzyme inhibition in heart failure. 1201 75