beta(3)-Adrenoceptors in the cardiovascular system: Putative roles in human pathologies

The sympathetic nervous system is central for the neurohumoral regulation of the cardiovascular system and is largely involved in many cardiovascular diseases affecting millions of people around the world. It is classically admitted that beta-adrenoceptors (beta-AR) of the beta(1) and beta(2) subtypes mediate the effects of catecholamines on the force of contraction of cardiac muscle, and on the relaxation of vascular smooth muscle. However, the molecular characterization in 1989 of a third beta-AR subtype, beta(3), and later its identification in human heart has changed the classically admitted paradigm on the regulation of heart function by the beta-adrenergic system. In blood vessels, beta(3)-AR, like beta(1) and beta(2), produced a relaxation. But at the present time, the physiological role of beta(3)-AR is not clearly identified. Thus, the purpose of this review is to summarize the pharmacological and molecular evidence supporting the functional roles of beta(3)-AR in cardiovascular tissues of various species, including humans. In addition, this review discusses the potential role of beta(3)-AR in several cardiovascular diseases and emphasizes their putative involvement as new therapeutic targets. (c) 2006 Elsevier Inc. All rights reserved.