Alpha-1-adrenergic receptors in heart failure: The adaptive arm of the cardiac response to chronic catecholamine stimulation

Brian C. Jensen, Timothy D. O'Connell, Paul C. Simpson

Research output: Contribution to journalReview article

35 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)291-301
Number of pages11
JournalJournal of Cardiovascular Pharmacology
Volume63
Issue number4
DOIs
StatePublished - Apr 2014

Keywords

  • 1-adrenergic receptors
  • cardioprotection
  • heart
  • heart failure
  • hypertrophy
  • ischemic preconditioning

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