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

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Book cover Cardiac Mechanics and Function in the Normal and Diseased Heart

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Summary

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.

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Authors and Affiliations

  1. Department of Medicine, University of California, San Francisco, USA

    Joel S. Karliner

  2. Cardiology Section, Veterans Administration Medical Center, San Francisco, CA, 94121, USA

    Joel S. Karliner

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  1. Joel S. Karliner
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Editors and Affiliations

  1. The First Department of Medicine, Osaka University School of Medicine, Fukushima-ku, Osaka, 553, Japan

    Masatsugu Hori

  2. Department of Cardiovascular Dynamics, National Cardiovascular Center Research Institute, Suita, Osaka, 565, Japan

    Hiroyuki Suga

  3. Laboratory of Clinical Physiology, Department of Cardiology, Leiden University Hospital, Leiden, The Netherlands

    Jan Baan

  4. Department of Cardiothoracic Surgery and Department of Physiology and Biophysics, Albert Einstein College of Medicine, Yeshiva University, The Bronx, NY, 10461, USA

    Edward L. Yellin

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© 1989 Springer-Verlag Tokyo

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Karliner, J.S. (1989). Adrenergic Receptors and Signal Transduction in Myocardial Hypertrophy, Ischemia, and Failure. In: Hori, M., Suga, H., Baan, J., Yellin, E.L. (eds) Cardiac Mechanics and Function in the Normal and Diseased Heart. Springer, Tokyo. https://doi.org/10.1007/978-4-431-67957-8_31

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  • DOI: https://doi.org/10.1007/978-4-431-67957-8_31

  • Publisher Name: Springer, Tokyo

  • Print ISBN: 978-4-431-68020-8

  • Online ISBN: 978-4-431-67957-8

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