The effects of long-term treatment with a novel angiotensin I converting enzyme (ACE) inhibitor, trandolapril, on ACE activity and cardiac function in rats with chronic heart failure (CHF) were examined and compared with those of captopril and enalapril. Left coronary artery ligation of rats resulted in decreases in mean arterial pressure, left ventricular systolic pressure, dP/dt, cardiac output and stroke volume indices, and increases in left ventricular end-diastolic pressure and systemic vascular resistance 12 weeks after the operation. A significant increase in ACE activity of the myocardium, but not that of serum or other tissues, was detected in the CHF rat 12 weeks after the operation. Oral treatment with ACE inhibitors (10 mg/kg/day captopril, 10 mg/kg/day enalapril or 3 mg/kg/day trandolapril) from the 2nd to 12th week, attenuated the changes in cardiac output and stroke volume indices, left ventricular end-diastolic pressure and systemic vascular resistance of the CHF rat. Treatment also attenuated the increase in the cardiac. ACE activity of CHF rats. A close relationship between the decrease in cardiac output index and the increase in cardiac ACE activity was detected. The results suggest that trandolapril, like other ACE inhibitors, exerts a beneficial effect on cardiac function in the CHF rat and that one of the mechanisms for this effect is attenuation of elevated cardiac ACE activity.
Angiotensin-Converting Enzyme Inhibitors Animals