Decreased Catecholamine Sensitivity and β-Adrenergic-Receptor Density in Failing Human Hearts

TLDR

The study examined β‑adrenergic‑receptor density, adenylate cyclase and creatine kinase activities, in vitro muscle contraction, and contractile protein levels in left ventricles of failing versus normal hearts from transplant recipients or donors to elucidate the role of the myocardial β‑adrenergic pathway in congestive heart failure. Failing hearts showed a 50–56 % drop in β‑adrenergic‑receptor density, a 45 % reduction in maximal isoproterenol‑stimulated adenylate cyclase activity, and a 54–73 % decline in isoproterenol‑stimulated muscle contraction, while other enzymatic activities and contractile protein levels were unchanged, indicating that reduced β‑receptor density causes β‑adrenergic subsensitivity and impaired contractility. N Engl J Med 1982; 307:205–11.

Abstract

To identify the role of the myocardial β-adrenergic pathway in congestive heart failure, we examined β-adrenergic-receptor density, adenylate cyclase and creatine kinase activities, muscle contraction in vitro, and myocardial contractile protein levels in the left ventricles of failing and normally functioning hearts from cardiac-transplant recipients or prospective donors. Eleven failing left ventricles had a 50 to 56 per cent reduction in β-receptor density, a 45 per cent reduction in maximal isoproterenol-mediated adenylate cyclase stimulation, and a 54 to 73 per cent reduction in maximal isoproterenol-stimulated muscle contraction, as compared with six normally functioning ventricles (P<0.05 for each comparison). In contrast, cytoplasmic creatine kinase activity, adenylate cyclase activities stimulated by fluoride ion and by histamine, histamine-stimulated muscle contraction, and levels of contractile protein were not different in the two groups (P>0.05). We conclude that in failing human hearts a decrease in β-receptor density leads to subsensitivity of the β-adrenergic pathway and decreased β-agonist-stimulated muscle contraction. Regulation of β-adrenergic receptors may be an important variable in cardiac failure. (N Engl J Med. 1982; 307:205–11.)