| Distribution of myocardial beta-adrenoceptor subtypes and coupling to the adenylate cyclase in children with congenital heart disease and implications for treatment. | |
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MedLine Citation:
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PMID: 8396157 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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In congestive heart failure, down-regulation of myocardial beta-adrenoceptors (beta-AR) due to an elevated sympathetic tone is well known. In infancy and childhood, heart failure is usually related to congenital heart disease (CHD). Therefore, 71 samples of right atrial tissue of infants and children with CHD undergoing cardiac surgery were studied for beta-adrenoceptor density and distribution of the beta 1-/beta 2-AR subtypes. In 49 cases, the coupling of the beta-AR to the adenylate cyclase (AC) was examined. In a further study of 19 myocardial samples, AC was selectively stimulated with beta 1- or beta 2-AR whereas the other subtype was blocked by an antagonist. The following results were obtained: (1) Infants and children with severe acyanotic or cyanotic CHD had severely reduced beta-AR densities. (2) In most of the cases, the beta-AR down regulation is beta 1-subtype selective, but in critically ill newborns with congenital aortic valve stenosis or transposition of the great arteries, there is additional significant beta 2-AR down-regulation. In Fallot patients treated with the beta-antagonist propranolol, a significant increased beta-AR number compared with untreated Fallot patients was found. (3) beta-Adrenoceptor reduction in CHD is correlated with elevated noradrenaline plasma levels, thus proving a sympathetic dysregulation. (4) In CHD with moderate hemodynamic load, beta 2-AR coupling to AC was markedly more efficient than beta 1-AR coupling. The small number of myocardial beta 2-AR produced most of the cyclic adenosine monophosphate. (5) In severe acyanotic and cyanotic CHD, a partial decoupling of the beta 2-AR to the AC occurred.(ABSTRACT TRUNCATED AT 250 WORDS) |
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Authors:
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R Kozlik-Feldmann; H H Kramer; H Wicht; R Feldmann; H Netz; D Reinhardt |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Journal of clinical pharmacology Volume: 33 ISSN: 0091-2700 ISO Abbreviation: J Clin Pharmacol Publication Date: 1993 Jul |
Date Detail:
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Created Date: 1993-10-07 Completed Date: 1993-10-07 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 0366372 Medline TA: J Clin Pharmacol Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 588-95 Citation Subset: IM |
Affiliation:
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Children's Hospital, Ludwig-Maximilians-University of Munich, Germany. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adenylate Cyclase
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analysis,
metabolism* Adolescent Animals Child Child, Preschool Down-Regulation Heart Atria / pathology Heart Defects, Congenital / drug therapy, enzymology* Humans Infant Infant, Newborn Myocardium / metabolism*, pathology Norepinephrine / blood Propranolol / therapeutic use Receptors, Adrenergic, beta / drug effects, metabolism* |
| Chemical | |
Reg. No./Substance:
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0/Receptors, Adrenergic, beta; 51-41-2/Norepinephrine; 525-66-6/Propranolol; EC 4.6.1.1/Adenylate Cyclase |
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