β3-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 β-adrenoceptors (β-AR) of the β1 and β2 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 β-AR subtype, β3, and later its identification in human heart has changed the classically admitted paradigm on the regulation of heart function by the β-adrenergic system. In blood vessels, β3-AR, like β1 and β2, produced a relaxation. But at the present time, the physiological role of β3-AR is not clearly identified. Thus, the purpose of this review is to summarize the pharmacological and molecular evidence supporting the functional roles of β3-AR in cardiovascular tissues of various species, including humans. In addition, this review discusses the potential role of β3-AR in several cardiovascular diseases and emphasizes their putative involvement as new therapeutic targets.