The use of beta3-adrenergic receptor agonists in the treatment of heart failure.
As the beta3-adrenergic receptor (beta3-AR) mediates a negative inotropic effect, upregulation of this receptor in patients with heart failure is considered to be harmful and associated with disease progression. The development of beta3-AR antagonists has therefore been proposed as a potential therapeutic option for heart failure. However, as increased intracellular myocyte Na+ levels represent a key adverse pathophysiological feature of heart failure, and the beta3-AR mediates the stimulation of the only export route for Na+ - the Na+-K+ pump - the upregulation of this receptor may also represent a useful compensatory mechanism. Data from animal studies and circumstantial observations from clinical trials suggest that beta3-AR activation is beneficial in severe heart failure, and that beta3-AR agonists are a promising therapeutic option for the treatment of this disease.
Rasmussen
Helge H
HH
Royal North Shore Hospital, Department of Cardiology, St Leonards, New South Wales 2065, Australia. helger@med.usyd.edu.au
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Gemma A
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Krum
Henry
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Bundgaard
Henning
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D000318:Adrenergic beta-Agonists / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use*; D000818:Animals; D002986:Clinical Trials as Topic; D006333:Heart Failure / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D009200:Myocardial Contraction / Q000187:drug effects; D022702:Receptors, Adrenergic, beta-3 / Q000235:genetics / Q000378:metabolism*
D000318:Adrenergic beta-Agonists; D022702:Receptors, Adrenergic, beta-3