Review ArticleEvolving Mechanisms of Action of Beta Blockers: Focus on NebivololMason, R Preston PhD*†; Giles, Thomas D MD‡; Sowers, James R MD§Author Information From the *Cardiovascular Division, Department of Medicine Brigham & Women's Hospital, Harvard Medical School, Boston, MA; †President and Founder, Elucida Research, Beverly, MA; ‡Department of Cardiology, Tulane University School of Medicine, New Orleans, LA; and §Professor of Medicine and Physiology Endocrinology, Diabetes & Metabolism, University of Missouri-Columbia, Columbia, MO. Received for publication July 22, 2008; accepted May 1, 2009. Supported by Forest Laboratories. The authors report no conflicts of interest. Reprints: R. Preston Mason, PhD, Elucida Research, PO Box 7100, Beverly, MA 01915 (e-mail: [email protected]rch.com). Journal of Cardiovascular Pharmacology: August 2009 - Volume 54 - Issue 2 - p 123-128 doi: 10.1097/FJC.0b013e3181ad207b Buy Metrics 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. © 2009 Lippincott Williams & Wilkins, Inc.