Decreased adrenergic neuronal uptake activity in experimental right heart failure. A chamber-specific contributor to beta-adrenoceptor downregulation
| Autor: | T.-H. M. Fan, Chang-Seng Liang, J. T. Sullebarger, S. Sakamoto |
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| Rok vydání: | 1989 |
| Předmět: |
medicine.medical_specialty
Renal cortex Down-Regulation Tyramine Adrenergic In Vitro Techniques Norepinephrine chemistry.chemical_compound Catecholamines Dogs Internal medicine Homologous desensitization medicine.artery Receptors Adrenergic beta medicine Animals Heart Failure Neurons biology Chemistry Myocardium Fissipedia Hemodynamics General Medicine biology.organism_classification medicine.disease medicine.anatomical_structure Endocrinology Ventricle Dihydroalprenolol Heart failure Pulmonary artery Research Article |
| Zdroj: | Journal of Clinical Investigation. 84:1267-1275 |
| ISSN: | 0021-9738 |
| DOI: | 10.1172/jci114294 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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