| Autor: |
Tavernier, Geneviève, Toumaniantz, Gilles, Erfanian, Mortéza, Heymann, Marie-France, Laurent, Karine, Langin, Dominique, Gauthier, Chantal |
| Předmět: |
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| Zdroj: |
Cardiovascular Research; Aug2003, Vol. 59 Issue 2, p288, 9p |
| Abstrakt: |
Objectives: The regulation of cardiac function by catecholamines involves three populations of β-adrenoceptor (β-AR). β1- and β2-AR stimulations produce an increase in contractility and β3-AR stimulation mediates a negative inotropic effect in human ventricular muscle. Because of the lack of suitable animal models, we have generated transgenic mice with cardiac-specific expression of the human β3-AR (TGβ3 mice). Methods: TGβ3 mice were produced by microinjection of the human β3-AR under the control of the α myosin heavy chain promoter. Phenotypic analyses comprised β3-AR mRNA and protein determinations, histological studies, electrocardiogram, contractility and cyclic nucleotide measurements. Results: TGβ3 mice presented no histological evidence of myocyte hypertrophy or fibrogenesis. In basal conditions, TGβ3 mice were characterized by an increase in heart rate and an acceleration of twitch parameters without modification of its amplitude. β3-AR agonists (CL 316243, SR 58611A) decreased contractility at low concentrations (1–100 nM). At high concentrations, the negative inotropic effect was abolished. Pretreatment with nadolol, a β1/β2-AR blocker, blunted the rebound in peak tension elicited by β3-AR agonists suggesting a non-specific action of these compounds on β1- and β2-AR. The involvement of β3-AR in the negative inotropic effect was confirmed by the pretreatment with bupranolol, a non-selective β-AR antagonist, which fully abolished the effects of SR 58611A. The negative inotropic effect was associated with an increase in intracellular cGMP level. Conclusions: We conclude that cardiac overexpression of β3-AR in mice reproduces ex vivo the negative inotropic effects obtained with β3-AR stimulation in human ventricular tissues. [Copyright &y& Elsevier] |
| Databáze: |
Complementary Index |
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