Pressure overload causes cardiac hypertrophy in β1- and β2-adrenergic receptor double knockout mice

Department of Drug Research and Evaluation, Istituto Superiore di Sanità, Consiglio Nazionale delle Ricerche, Rome, Italy.
Journal of Hypertension (Impact Factor: 4.72). 04/2006; 24(3):563-71. DOI: 10.1097/01.hjh.0000203843.41937.2a
Source: PubMed


Cardiac hypertrophy arises as an adaptive response to increased afterload. Studies in knockout mice have shown that catecholamines, but not alpha1-adrenergic receptors, are necessary for such an adaptation to occur. However, whether beta-adrenergic receptors are critical for the development of cardiac hypertrophy in response to pressure overload is not known at this time.
Pressure overload was induced by transverse aortic banding in beta1-adrenergic and beta2-adrenergic receptor double knockout (DbetaKO) mice, in which the predominant cardiac beta-adrenergic receptor subtypes are lacking. Chronic pressure overload for 4 weeks induced cardiac hypertrophy in both DbetaKO and wild-type mice. There were no significant differences between banded mice in left ventricular weight to body weight ratio, in the left ventricular wall thickness, in the cardiomyocyte size or in the expression levels of the load-sensitive cardiac genes such as ANF and beta-MHC. Additionally, the left ventricular systolic pressure, an index of afterload, and cardiac contractility, evaluated as dp/dtmax, the maximal slope of systolic pressure increment, and Ees, end-systolic elastance, were increased at a similar level in both wild-type and DbetaKO banded mice, and were significantly greater than in sham controls.
Despite chronic activation of the cardiac beta-adrenergic system being sufficient to induce a pathological hypertrophy, we show that beta1-adrenergic and beta2-adrenergic receptors are not an obligatory component of the signaling pathway that links the increased afterload to the development of cardiac hypertrophy.

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    • "The findings by Patrizio et al. (2007) would have been strengthened by providing measures of cardiomyocyte hypertrophy (such as cell size, protein synthesis), exploring potential signalling mechanisms and validating the results from pharmacological approaches by using genetically engineered models, such as b-adrenoceptor knockout mice. Actually, a recent paper from the same group found no difference between the b 1 -and b 2 -adrenoceptor dualknockout and wild-type mice in the extent of TACinduced hypertrophy, fetal gene expression and fibrosis (Palazzesi et al., 2006), findings contradictory to the current report (Patrizio et al., 2007). Furthermore, although hypertrophy was inhibited, b-blockade had no effect on the suppressed SERCA expression (Patrizio et al., 2007). "
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