Evolving Mechanisms of Action of Beta Blockers: Focus on Nebivolol

Abstract

Beta (β) blockers are widely used for treatment of cardiovascular and noncardiovascular diseases. Nevertheless, their mechanism of action is not fully understood and differs significantly among agents in this class. Chronic increases in adrenergic activity in heart failure result in desensitization of cardiac β-adrenergic receptor signal transduction and adverse effects on myocytes. By reducing heart rate and decreasing myocardial workload, the pathologic remodeling of the heart may be reversed with β-blocking agents. Among β-blockers, there are clear differences in pharmacodynamic and pharmacokinetic properties. Newer β-blockers differ from older agents with respect to β-adrenoceptor affinity and selectivity and partial agonist activity, which may affect their mechanism of action and be important in clinical use.The first β-antagonist compounds were nonselective; the next generation of β-blockers was selective for β₁-receptors_. The most recent β-blockers may be nonselective or selective, and they have the additional ancillary property of vasodilation. Nebivolol is among the newer third-generation β-blockers. It is unique in the class, since apart from its cardioselectivity, it also produces nitric oxide-mediated vasodilation. As a result, its hemodynamic profile is clearly different from those of traditional β-blockers. This review will evaluate this class of agents and the basis for their differences in clinical use.