Decreased adrenergic neuronal uptake activity in experimental right heart failure. A chamber-specific contributor to beta-adrenoceptor downregulation

J Clin Invest. 1989 Oct;84(4):1267-75. doi: 10.1172/JCI114294.


The reduction of myocardial beta-adrenoceptor density in congestive heart failure has been thought to be caused by agonist-induced homologous desensitization. However, recent evidence suggests that excessive adrenergic stimulation may not produce myocardial beta-receptor downregulation unless there is an additional defect in the local norepinephrine (NE) uptake mechanism. To investigate the association between beta-adrenoceptor regulation and NE uptake activity, we carried out studies in 30 dogs with right heart failure (RHF) produced by tricuspid avulsion and progressive pulmonary artery constriction and 23 sham-operated control dogs. We determined NE uptake activity by measuring accumulation of [3H]NE in tissue slices, NE uptake-1 carrier density by [3H]mazindol binding and beta-adrenoceptor density by [3H]dihydroalprenolol binding. Compared with sham-operated dogs, RHF dogs showed a 26% decrease in beta-adrenoceptor density, a 51% reduction in NE uptake activity, and a 57% decrease in NE uptake-1 carrier density in their right ventricles. In addition, right ventricle beta-receptor density correlated significantly with NE uptake activity and NE uptake-1 carrier density. In contrast, neither NE uptake activity nor beta-receptor density in the left ventricle and renal cortex was affected by RHF. Thus, the failing myocardium is associated with an organ- and chamber-specific subnormal neuronal NE uptake. This chamber-specific loss of NE uptake-1 carrier could effectively reduce local NE clearance, and represent a local factor that predisposes the failing ventricle to beta-adrenoceptor downregulation.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Catecholamines / analysis
  • Catecholamines / blood
  • Dogs
  • Down-Regulation*
  • Heart Failure / metabolism
  • Heart Failure / physiopathology*
  • Hemodynamics
  • In Vitro Techniques
  • Myocardium / metabolism
  • Neurons / metabolism
  • Neurons / physiology*
  • Norepinephrine / metabolism
  • Receptors, Adrenergic, beta / metabolism
  • Receptors, Adrenergic, beta / physiology*
  • Tyramine / pharmacology


  • Catecholamines
  • Receptors, Adrenergic, beta
  • Norepinephrine
  • Tyramine