Carvedilol inhibits mitochondrial oxygen consumption and superoxide production during calcium overload in isolated heart mitochondria.

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 Ca(2+) overload was investigated.

Methods And Results: The mitochondrial oxygen consumption (mVO(2)) and the mitochondrial ROS production in isolated rat heart mitochondria was measured. Ca(2+) overload from 10 to 100 micromol/L augmented mVO(2) was from 527+/-139 to 671 +/-138 nmol/mg (p<0.05), and this was then completely suppressed by carvedilol (1 micromol/L), but not by metoprolol (100 micromol/L). Ca(2+) 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 mVO(2) 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.