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European Heart Journal 1996 17(Supplement B):8-16; doi:10.1093/eurheartj/17.suppl_B.8
Copyright © 1996 by the European Society of Cardiology.
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© 1996 1996 The European Society of Cardiology

Cardiac adrenergic receptor effects of carvedilol

T. Yoshikawa, J. D. Port, K. Asano, P. Chidiak, M. Bouvier, D. Dutcher, R. L. Roden, W. Minobe, K. D. Tremmel and M. R. Bristow

Division of Cardiology, The Temple Hoyne Buell Heart Research Laboratories, University of Colorado Health Sciences Center, U.S.A.

Correspondence: Michael R. Bristow, MD, PhD, University of Colorado, Health Sciences Center, Cardiology, B-139, 4200 East Ninth Avenue, Denver, Colorado 80262, U.S A.

Carvedilol is an adrenoceptor antagonist which modulates the activity not only of β1 and β1 but also of {alpha}1 adrenergic receptors present on the cell surface membrane of the human cardiac myocyte. In the heart, carvedilol has approximately 7 times higher potency for 13, and 132 adrenoceptors, but in the doses 50–100 mg. day–1 used in clinical practice, it is essentially non-selective. In human myocardial preparations and in cultured heart cells, carvedilol has no intrinsic sympathomimetic activity but is able to identify high affinity agonist-binding receptors whose pharmaco logical signature is reduction in binding by incubation with guanine nucleotides (guanine nucleotide-modulatable binding). This property is more prominent for the human β2 than for the β1adrenoceptor. The property of gaunine nucleotide-modulatable binding for carvedilol and structurally related bucindolol correlates with their ability to directly down-regulate β1-like receptors present in cultured chick myocytes, and with a lack of reversal of down-regulation of cardiac β-receptors in patients with heart failure. Carvedilol does not exhibit high levels of inverse agonist activity, which may contribute to its good tolerability in subjects with heart failure.

These data indicate that carvedilol produces a high degree of adrenergic receptor blockade in the failing human heart, and does not re-sensitize the β-receptor pathway to stimulation by adrenergic agonists.

Key Words: Cardiac adrenoceptors • {alpha}-blockade • {alpha}-blockade • carvedilol • heart failure


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Myocardial beta-1 adrenoceptor down-regulation in aging and heart failure: implications for beta-blocker use in older adults with heart failure
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[Abstract] [Full Text] [PDF]


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