Effects of Afterload-Reducing Drugs on Pathogenesis of Antioxidant Changes and Congestive Heart Failure in Rats

Objectives. The present study sought to evaluate the effects of the afterload-reducing drugs captopril and prazosin on changes in antioxidants as well as oxidative stress in relation to hemodynamic function in congestive heart failure (CHF) subsequent to myocardial infarction (MI). Background. Afterload reduction therapy has been shown to reduce morbidity and mortality in patients with MI. CHF subsequent to MI in rats is associated with decrease in myocardial endogenous antioxidants and an increase in oxidative stress. Methods. The left anterior descending coronary artery in male Sprague-Dawley rats was ligated. Sham and experimental (postMI [PMI]) animals were assessed for hemodynamic function as well as lung and liver weights at 1, 4 and 16 weeks after operation. At 4 weeks, some rats were also treated with captopril (2 g/liter in drinking water daily) or prazosin (0.2 mg/kg body weight subcutaneously daily) and assessed at 16 weeks. Hearts were isolated to study the activity of superoxide dismutase (SOD), glutathione peroxidase (GSHPx) and catalase as well as for thiobarbituric acid reactive substances (TBARS). Results. CHF at 4 and 16 weeks in the infarcted rats was indicated by an increase in left ventricular end-diastolic pressure and wet/dry weight lung and liver ratios and depressed left ventricular systolic pressure and dyspnea. All these changes were attenuated in both the captopril- and prazosin-treated groups. SOD, GSHPx and catalase activity in the untreated PMI groups was decreased at 4 and 16 weeks. However, treatment with captopril resulted in significant improvement in SOD, GSHPx and catalase activity in the 16-week PMI group. With prazosin, only SOD activity was improved in the treated 16-week PMI group. Lipid peroxidation as indicated by TBARS was significantly increased in the 16-week PMI group, and both captopril and prazosin modulated this increase. Conclusions. Occurrence of an antioxidant deficit and an increase in oxidative stress in the myocardium may play role in the pathogenesis of CHF subsequent to MI. Attenuation of these changes in antioxidant activity with vasodilator (or antioxidant?) therapy mitigates the process of heart failure.