Abstract
The mechanism that leads to a decrease in β(1)-adrenergic receptor (β(1)AR) expression in the failing heart remains uncertain. This study shows that cardiomyocyte β(1)AR expression and isoproterenol responsiveness decrease in response to oxidative stress. Studies of mechanisms show that the redox-dependent decrease in β(1)AR expression is uniquely prevented by carvedilol and not other βAR ligands. Carvedilol also promotes the accumulation of N-terminally truncated β(1)ARs that confer protection against doxorubicin-induced apoptosis in association with activation of protein kinase B. The redox-induced molecular controls for cardiomyocyte β(1)ARs and pharmacologic properties of carvedilol identified in this study have important clinical and therapeutic implications.