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European Heart Journal 1993 14(10):1349-1353;
Copyright © 1993 by the European Society of Cardiology.
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© 1993 The Europen Society of Cardiology

Down-regulation of ß-adrenergic receptors on mononuclear leukocytes induced by dobutamine treatment in patients with congestive heart failure

J.-K. TENG, C.-M. KWAN, L.-J. LIN, L.-M. TSAI, J.-T. CHENG*, W.-C. CHANG* and J.-H. CHEN

Division of Cardiology, Department of Internal Medicine, National Cheng Kung University Medical College and Hospital Tainan 70428, Taiwan
*Department of Pharmacology, National Cheng Kung University Medical College and Hospital Tainan 70428, Taiwan

Received 6 November 1992; revised 15 March 1993; .

Correspondence: Dr Jyh-Hong Chen, Department of Internal Medicine, National Cheng Kung University Hospital, 138, Shing-Li Road, Tainan 70428, Taiwan.

Abstract

(±)-Dobutamine is a positive inotropic drug usually used to improve ventricular function in patients with congestive heart failure (CHF). However, it has been found that haemodynamic responses to dobutamine become blunted during continuous treatment. In this study we determined the time-dependent changes of ß-adrenergic receptors in CHF patients treated with dobutamine. Seven CHF patients received a continuous intravenous infusion of dobutamine (5 µg.kg–1. min–1) for 96 h. Blood samples were obtained before and every 24 h after starting the therapy. The density of ß-adrenergic receptors on mononuclear leukocytes and the plasma concentrations of norepinephrine and epinephrine were determined. During dobutamine treatment the receptor density (fmol.mg–1, mean±SEM) gradually decreased from 42.8±4.4 (baseline) to 31.4±3.3 (P<0.05), 25.2±4.0 (P<0.01), 18.8±5.5 (P<0.01) and 13.4±3.4 (P<0.01) at 24, 48, 72 and 96 h, respectively. However, the plasma concentrations of norepinephrine and epinephrine were not significantly changed during the 96 h period of treatment. Thus, the ß-adrenergic receptors down-regulated as early as 24 h after the dobutamine treatment was begun in CHF patients. This receptor down-regulation was not associated with changes of plasma catechol-amine concentrations, but was related rather to the development of drug tolerance to dobutamine.

Key Words: ß-adrenergic receptor • down-regulation • dobutamine • congestive heart failure • drug tolerance


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