title: Alpha-1-adrenergic receptors in heart failure: the adaptive arm of the cardiac response to chronic catecholamine stimulation.
abstract: Alpha-1-adrenergic receptors (ARs) are G protein-coupled receptors activated by catecholamines. The alpha-1A and alpha-1B subtypes are expressed in mouse and human myocardium, whereas the alpha-1D protein is found only in coronary arteries. There are far fewer alpha-1-ARs than beta-ARs in the nonfailing heart, but their abundance is maintained or increased in the setting of heart failure, which is characterized by pronounced chronic elevation of catecholamines and beta-AR dysfunction. Decades of evidence from gain and loss-of-function studies in isolated cardiac myocytes and numerous animal models demonstrate important adaptive functions for cardiac alpha-1-ARs to include physiological hypertrophy, positive inotropy, ischemic preconditioning, and protection from cell death. Clinical trial data indicate that blocking alpha-1-ARs is associated with incident heart failure in patients with hypertension. Collectively, these findings suggest that alpha-1-AR activation might mitigate the well-recognized toxic effects of beta-ARs in the hyperadrenergic setting of chronic heart failure. Thus, exogenous cardioselective activation of alpha-1-ARs might represent a novel and viable approach to the treatment of heart failure.
authors.affiliation: *Division of Cardiology and McAllister Heart Institute, University of North Carolina, Chapel Hill, NC; †Department of Integrative Biology and Physiology, University of Minnesota, Minneapolis, MN; and ‡Division of Cardiology, VA Medical Center, Cardiovascular Research Institute, and Department of Medicine, University of California, San Francisco, CA.
authors.forename: Brian C
authors.initials: BC
authors.lastname: Jensen
authors.forename: Timothy D
authors.initials: TD
authors.lastname: OʼConnell
authors.forename: Paul C
authors.initials: PC
authors.lastname: Simpson
mesh_terms: D058668:Adrenergic alpha-1 Receptor Antagonists / Q000009:adverse effects; D000818:Animals; D002395:Catecholamines / Q000502:physiology*; D006321:Heart / Q000503:physiopathology*; D006333:Heart Failure / Q000188:drug therapy / Q000235:genetics / Q000503:physiopathology*; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D018340:Receptors, Adrenergic, alpha-1 / Q000145:classification / Q000187:drug effects / Q000235:genetics / Q000502:physiology*
chemical_list: D058668:Adrenergic alpha-1 Receptor Antagonists; D002395:Catecholamines; D018340:Receptors, Adrenergic, alpha-1