Characterization of lymphocyte beta-adrenergic receptors at rest and during exercise in ambulatory patients with chronic congestive heart failure

Abstract

To investigate β-adrenergic receptor dysfunction in congestive heart failure (CHF), the density of lymphocyte β receptors and adenylate cyclase activity was measured at rest and at peak exercise in 30 patients with CHF and 7 age-matched control subjects. At rest, patients with CHF had reduced β-receptor density (normals 33 ± 2; CHF 21 ± 2 fmol/ mg protein; p < 0.01) and isoproterenol-stimulated adenylate cyclase activity (normals 50 ± 9; CHF 28 ± 4 pmol/mg protein/min; p < 0.05). Sodium fluoride-stimulated adenylate cyclase activity was also reduced (normals 98 ± 17; CHF 48 ± 12 pmol/mg protein/min; p < 0.01). In the patients with CHF, there was no significant correlation between receptor density and peak exercise VO 2, ejection fraction or resting plasma catecholamines. In the normal subjects, maximal exercise increased β-receptor density by 100% (rest 33 ± 2; exercise 67 ± 7 fmol/mg protein) and isoproterenol-stimulated adenylate cyclase activity by 66% (rest 50 ± 9; exercise 83 ± 18 pmol/mg protein/min (both p < 0.01)). In contrast, patients with CHF exhibited only a 58% increase in β-receptor density (rest 20 ± 3; exercise 32 ± 6 fmol/mg protein; p < 0.01) and no significant change in isoproterenol-stimulated adenylate cyclase activity (rest 27 ± 5; exercise 24 ± 5 pmol/mg protein/min). These findings suggest that (1) CHF is associated with reduced density of β receptors and either uncoupling of guanine nucleotide regulatory binding protein from adenylate cyclase or defective cyclase; (2) β-receptor density in CHF is not a simple function of ejection fraction, functional capacity or circulating catecholamines; and (3) exercise produces desensitization or uncoupling of the β receptor from adenylate cyclase in CHF.