The distinct effect of carvedilol and metoprolol on the mitochondrial superoxide production under calcium overload of myocardium

Abstract

Purpose: In heart failure or ischemia-reperfusion injury, intracellular calcium overload occurs in the myocardium. However, mitochondrial functions during calcium overload are not well known. Additionally failing myocardium have source of oxygen free radicals from mitochondrial electron transport complex 1. Recently, a beta-blocker is known to be useful for heart failure, and also suggested the difference between the drugs depending on the lipid solubility, and with or without antioxidant effect. Methods: Isolated mitochondria from SD rat hearts were loaded in the cuvette mounted by Clark oxygen sensor to measure the mitochondrial oxygen consumption. The amount of malondialdehyde (MDA) was measured as an index of superoxide production. Calcium concentration was varied at 10, 100 μM and carvedilol and metoprolol concentration was varied at 1, 10, 100 μM. Rotenone was used for injuring complex 1. Result: The oxygen consumption was significantly augmented by increasing the calcium concentration from 10 to 100 μM (p < 0.05). This increase of oxygen consumption was significantly suppressed by even 1 μM carvedilol (p < 0.05), but not metoprolol. The amount of MDA was augmented by rotenone (p < 0.01). This increase of MDA was suppressed by carvedilol dose dependently (p < 0.05), but not metoprolol. Conclusion: These data strongly suggest the distinct effect of carvedilol on superoxide production and oxygen consumption from metoprolol, which may be beneficial for the protection of cardiomyocyte from oxidant stress.