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

(+/-)-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 beta-adrenergic receptors in CHF patients treated with dobutamine. Seven CHF patients received a continuous intravenous infusion of dobutamine (5 micrograms.kg-1 x min-1) for 96 h. Blood samples were obtained before and every 24 h after starting the therapy. The density of beta-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 beta-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 catecholamine concentrations, but was related rather to the development of drug tolerance to dobutamine.