Abstract
Background The COMET study suggested the better effect of carvedilol to metoprolol in treating heart failure. However, its underlying mechanisms of action remain unclear. As a result, evaluation of the distinct effects of both drugs on the mitochondrial function and reactive oxygen species (ROS) production during Ca2+ overload was investigated. Methods and Results The mitochondrial oxygen consumption (mVO2) and the mitochondrial ROS production in isolated rat heart mitochondria was measured. Ca2+ overload from 10 to 100 μmol/L augmented mVO2 was from 527±139 to 671 ±138 nmol/mg (p<0.05), and this was then completely suppressed by carvedilol (1 μmol/L), but not by metoprolol (100 μmol/L). Ca2+ overload augmented the ROS production upon complex I injury (9.7±1.2 to 11.4±1.4 nmol/mg, p<0.05). Carvedilol dose-dependently suppressed this ROS production, whereas metoprolol did not. Conclusions Carvedilol, but not metoprolol, was thus found to inhibit the calcium-dependent augmentation of mVO2 and ROS production upon complex I injury. This new effect of carvedilol might partly explain the beneficial effect of carvedilol for the treatment of heart failure. (Circ J 2006; 70: 321 - 326)
