Summary
The progression of changes in β-adrenergic receptor signalling was studied over several time points during the development of pacing-induced heart failure in long-term instrumented, conscious dogs. Animals were paced at 240 beats per minute for one month and data were averaged at 1 day, 1 week, and 3–4 weeks after pacing. The rate of change in left ventricular pressure (LV dP/dt) was decreased at 1 day, LV end-diastolic pressure and heart rate were increased at 1 week, but heart failure occurred only after 3–4 weeks of pacing. Circulating levels of norepinephrine were elevated after 1 day of pacing, and tissue levels of norepinephrine were reduced only after 3–4 weeks of pacing. High-affinity β-adrenergic receptors and adenylyl cyclase activity decreased after one day of pacing. β1-adrenergic receptor density decreased after one week of pacing. Gs functional activity was not reduced, but Giα2 rose after 3–4 weeks of pacing. Thus, β-adrenergic receptor signal transduction is significantly altered early, i. e., 1 day after the initiation of rapid ventricular pacing, prior to the development of heart failure. Changes occurring at 1 day after rapid ventricular pacing include increases in plasma catecholamines, uncoupling of the β-adrenergic receptor from adenylyl cyclase, and a decrease in adenylyl cyclase activity. After more prolonged pacing there is a decrease in β1-adrenergic receptors, decreases in myocardial tissue catecholamines, and increases in Giα2. Therefore, physiological changes in β-adrenergic receptor function during the initial development of heart failure appear to be mediated by different mechanisms than those changes that occur later as heart failure becomes manifest.
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© 1994 Springer Japan
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Vatner, D.E. (1994). Abnormalities in β-Adrenergic Signal Transduction with Myocardial Decompensation and Failure. In: Hori, M., Maruyama, Y., Reneman, R.S. (eds) Cardiac Adaptation and Failure. Springer, Tokyo. https://doi.org/10.1007/978-4-431-67014-8_14
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DOI: https://doi.org/10.1007/978-4-431-67014-8_14
Publisher Name: Springer, Tokyo
Print ISBN: 978-4-431-67016-2
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