title: Beta-3 adrenoceptors as new therapeutic targets for cardiovascular pathologies.
abstract: Catecholamines play a key role in the regulation of cardiovascular function, classically through ß(1/2)-adrenoreceptors (AR) activation. After ß(3)-AR cloning in the late 1980s, convincing evidence for ß(3)-AR expression and function in cardiovascular tissues recently initiated a reexamination of their involvement in the pathophysiology of cardiovascular diseases. Their upregulation in diseased cardiovascular tissues and resistance to desensitization suggest they may be attractive therapeutic targets. They may substitute for inoperant ß(1/2)-AR to mediate vasodilation in diabetic or atherosclerotic vessels. In cardiac ventricle, their contractile effects are functionally antipathetic to those of ß(1/2)-AR; in normal heart, ß(3)-ARs may mediate a moderate negative inotropic effect, but in heart failure, it may protect against adverse effects of excessive catecholamine stimulation by action on excitation-contraction coupling, electrophysiology, or remodelling. Thus, prospective studies in animals and patients at different stages of heart failure should lead to identify the best therapeutic window to use ß(3)-AR agonists and/or antagonists.
authors.affiliation: INSERM, UMR-915, l'institut du thorax, F-44000, Nantes, France. chantal.gauthier@univ-nantes.fr
authors.forename: Chantal
authors.initials: C
authors.lastname: Gauthier
authors.forename: Bertrand
authors.initials: B
authors.lastname: Rozec
authors.forename: Boris
authors.initials: B
authors.lastname: Manoury
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Balligand
mesh_terms: D058667:Adrenergic beta-3 Receptor Agonists / Q000494:pharmacology*; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000375:Aging / Q000502:physiology; D000818:Animals; D002319:Cardiovascular System / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D003920:Diabetes Mellitus / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology; D006333:Heart Failure / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D006973:Hypertension / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D007037:Hypothyroidism / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D008103:Liver Cirrhosis / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D023421:Models, Animal; D009200:Myocardial Contraction / Q000187:drug effects / Q000502:physiology; D009203:Myocardial Infarction / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D022702:Receptors, Adrenergic, beta-3 / Q000502:physiology*; D018805:Sepsis / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D020257:Ventricular Remodeling
chemical_list: D058667:Adrenergic beta-3 Receptor Agonists; D000319:Adrenergic beta-Antagonists; D022702:Receptors, Adrenergic, beta-3