Oxygen Radical System in Chronic Infarcted Rat Heart: The Effect of Combined Beta Blockade and ACE Inhibition

Abstract

In vitro experiments suggest that beta blockade and angiotensin-converting enzyme (ACE) inhibition may protect the failing heart by reduction of myocardial oxidative stress. To test this hypothesis in an in vivo model, the beta blocker metoprolol (350 mg) and the ACE inhibitor ramipril (1 mg) were given either alone or in combination to rats (per kilogram body weight per day) for 6 weeks after myocardial infarction. Left ventricular end-diastolic pressure (LVEDP), contractile function of papillary muscles, enzymatic antioxidative defense (indicated by the activities of the superoxide dismutase isoenzymes and glutathione peroxidase), and the extent of lipid peroxidation were studied. Placebo-treated rats showed cardiac hypertrophy, increased LVEDP, lower rates of contraction and relaxation, as well as a deficit in the myocardial antioxidative defense associated with increased lipid peroxide levels, when compared with sham-operated animals. Combined beta blockade and ACE inhibition improved the antioxidative defense, reduced hypertrophy and LVEDP, and enhanced rates of contraction. Thus prolonged beta blockade and ACE inhibition after infarction may decrease myocardial oxidative stress and thereby could be beneficial in heart failure.

Anti-oxidative stress effects of Herba leonuri on ischemic rat hearts

“…Hill and Singal (1996) evaluated antioxidant enzyme activities and oxidative stress in the myocardium for 16 weeks after myocardial infarction in rats, and found that SOD, GPx and CAT activities decreased gradually but significantly 4 weeks after myocardial infarction, in tandem with the continuing increase in TBARs. Such results were similar to those found by Theres et al (2000). Our findings combined with those studies give a clear picture of the changes in the endogenous antioxidant system under conditions of oxidative stress.…”

Angiotensin II and Oxidative Stress in the Failing Heart

“…However, in AngII-treated rat cardiac fibroblasts, the activity of both MnSOD and Cu/ZnSOD was inhibited, and expression of MnSOD, but not Cu/ZnSOD, was decreased (59). Similarly, in rats subjected to MI, MnSOD expression in the infarct area and activity of both MnSOD and Cu/ZnSOD were reduced, and these decreases were suppressed by treatment with RAS inhibitors (127). In addition, nuclear SIRT1, which is increased in cardiomyocytes in several models of HF, upregulates MnSOD expression, leading to a reduction in ROS levels and apoptosis in AngII-treated C2C12 cells, as well as improved cardiac function and survival in hamsters with chronic HF (126).…”

Effects of the Angiotensin-converting Enzyme Inhibitor Enalapril on Sympathetic Neuronal Function and .BETA.-adrenergic Desensitization in Heart Failure after Myocardial Infarction in Rats.

“…Both the favorable alteration of the LV loading condition and suppression of the renin-angiotensin system by ACE inhibitors might attenuate LV remodeling and play an important role in the treatment of heart failure after MI. In addition, changes in cardiac gene expression, 46) and a reduction of myocardial oxidative stress 47) by ACE inhibitors have been reported. Some methodological limitations deserve comment when interpreting the present results.…”