Adrenergic Receptors and Signal Transduction in Myocardial Hypertrophy, Ischemia, and Failure

  • Joel S. Karliner


Signal transduction mediated by both α1- and β-adrenergic receptors may be important in the pathogenesis of myocardial hypertrophy, ischemia, and failure. In neonatal rat ventricular myocytes, α1-adrenergic agonism produces cardiac cell enlargement by mechanisms that ultimately involve regulation of genes controlling myocardial protein synthesis. In this system α1-adrenergic receptors do not down-regulate, and second messenger production (inositol trisphosphate) does not undergo desensitization. On the gene level, the rates of transcription of several genes are regulated in a highly complex manner which is currently under intense investigation. Both in animal models and in patients with congestive cardiac failure, down-regulation of β-adrenergic receptors appears to be a constant finding. This at least in part accounts for the reduction of adenylate cyclase activity and myocardial function that is observed. Recent attention has focused on the role of G proteins in heart failure. There appears to be an abnormality in G protein function but whether this results from a reduction in the guanine nucleotide stimulatory protein, Gs, or an increase in the guanine nucleotide inhibitory protein, Gi, or both, has not been established. In an animal model of acute myocardial ischemia, Gs function is diminished, but in the presence of chronic β-blockade there appears to be enhanced coupling between Gs and the β-adrenergic receptor resulting in relative preservation of agonist-stimulated adenylate cyclase activity, particularly in the subepicardium. This observation could account, at least in part, for the beneficial effects of chronic β-adrenergic blockade in acute myocardial ischemia.


Adrenergic Receptor Pertussis Toxin Adenylate Cyclase Activity Myocardial Hypertrophy Congestive Cardiac Failure 


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Copyright information

© Springer-Verlag Tokyo 1989

Authors and Affiliations

  • Joel S. Karliner
    • 1
    • 2
  1. 1.Department of MedicineUniversity of CaliforniaSan FranciscoUSA
  2. 2.Cardiology SectionVeterans Administration Medical CenterSan FranciscoUSA

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