The alpha(1A/C)- and alpha(1B)-adrenergic receptors are required for physiological cardiac hypertrophy in the double-knockout mouse.

Détails

ID Serval
serval:BIB_6AE48502B5DA
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
The alpha(1A/C)- and alpha(1B)-adrenergic receptors are required for physiological cardiac hypertrophy in the double-knockout mouse.
Périodique
Journal of Clinical Investigation
Auteur(s)
O'Connell T.D., Ishizaka S., Nakamura A., Swigart P.M., Rodrigo M.C., Simpson G.L., Cotecchia S., Rokosh D.G., Grossman W., Foster E., Simpson P.C.
ISSN
0021-9738 (Print)
ISSN-L
0021-9738
Statut éditorial
Publié
Date de publication
2003
Volume
111
Numéro
11
Pages
1783-1791
Langue
anglais
Résumé
Catecholamines and alpha(1)-adrenergic receptors (alpha(1)-ARs) cause cardiac hypertrophy in cultured myocytes and transgenic mice, but heart size is normal in single KOs of the main alpha(1)-AR subtypes, alpha(1A/C) and alpha(1B). Here we tested whether alpha(1)-ARs are required for developmental cardiac hypertrophy by generating alpha(1A/C) and alpha(1B) double KO (ABKO) mice, which had no cardiac alpha(1)-AR binding. In male ABKO mice, heart growth after weaning was 40% less than in WT, and the smaller heart was due to smaller myocytes. Body and other organ weights were unchanged, indicating a specific effect on the heart. Blood pressure in ABKO mice was the same as in WT, showing that the smaller heart was not due to decreased load. Contractile function was normal by echocardiography in awake mice, but the smaller heart and a slower heart rate reduced cardiac output. alpha(1)-AR stimulation did not activate extracellular signal-regulated kinase (Erk) and downstream kinases in ABKO myocytes, and basal Erk activity was lower in the intact ABKO heart. In female ABKO mice, heart size was normal, even after ovariectomy. Male ABKO mice had reduced exercise capacity and increased mortality with pressure overload. Thus, alpha(1)-ARs in male mice are required for the physiological hypertrophy of normal postnatal cardiac development and for an adaptive response to cardiac stress.
Mots-clé
Animals, Blotting, Western, Body Weight, Cells, Cultured, Dose-Response Relationship, Drug, Echocardiography, Female, Genotype, Heart/physiology, Hypertrophy/genetics, MAP Kinase Signaling System, Male, Mice, Mice, Knockout, Mice, Transgenic, Mitogen-Activated Protein Kinase 1/metabolism, Mitogen-Activated Protein Kinase 3, Mitogen-Activated Protein Kinases/metabolism, Muscle Cells/metabolism, Myocardial Contraction, Myocardium/metabolism, Organ Size, Physical Conditioning, Animal, Receptors, Adrenergic, alpha-1/genetics, Receptors, Adrenergic, alpha-1/physiology, Ribonucleases/metabolism, Sex Factors, Time Factors
Pubmed
Web of science
Open Access
Oui
Création de la notice
24/01/2008 11:05
Dernière modification de la notice
20/08/2019 14:25
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