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Propranolol causes a paradoxical enhancement of cardiomyocyte foetal gene response to hypertrophic stimuli.

Authors: Patrizio, M  Musumeci, M  Stati, T  Fasanaro, P  Palazzesi, S  Catalano, L  Marano, G 
Citation: Patrizio M, etal., Br J Pharmacol. 2007 Sep;152(2):216-22. Epub 2007 Jun 25.
Pubmed: (View Article at PubMed) PMID:17592507
DOI: Full-text: DOI:10.1038/sj.bjp.0707350

BACKGROUND AND PURPOSE: Pathological cardiac hypertrophy is associated with the expression of a gene profile reminiscent of foetal development. The non selective beta-adrenoceptor antagonist propranolol is able to blunt cardiomyocyte hypertrophic response in pressure-overloaded hearts. It remains to be determined whether propranolol also attenuates the expression of hypertrophy-associated foetal genes.
EXPERIMENTAL APPROACH: To address this question, the foetal gene programme, of which atrial natriuretic peptide (ANP), the beta-isoform of myosin heavy chain (beta-MHC), and the alpha-skeletal muscle isoform of actin (skACT) are classical members, was induced by thoracic aortic coarctation (TAC) in C57BL/6 mice, or by phenylephrine, a selective alpha(1)-adrenoceptor agonist, in cultured rat neonatal cardiomyocytes.
KEY RESULTS: In TAC mice, the left ventricular weight-to-body weight (LVW/BW) ratio increased by 35% after 2 weeks. Levels of ANP, beta-MHC and skACT mRNA in the left ventricles increased 2.2-fold, 2.0-fold and 12.1-fold, respectively, whereas alpha-MHC and SERCA mRNA levels decreased by approximately 50%. Although propranolol blunted cardiomyocyte growth, with approximately an 11% increase in the LVW/BW ratio, it enhanced the expression of ANP, beta-MHC and skACT genes (10.5-fold, 27.7-fold and 22.7-fold, respectively). Propranolol also enhanced phenylephrine-stimulated ANP and beta-MHC gene expression in cultured cardiomyocytes. Similar results were obtained with metoprolol, a selective beta(1)-adrenoceptor antagonist, but not with ICI 118551, a beta(2)-adrenoceptor antagonist.
CONCLUSIONS AND IMPLICATIONS: Propranolol enhances expression of the hypertrophy-associated foetal genes mainly via the beta(1)-adrenoceptor blockade. Our results also suggest that, in pressure-overloaded hearts, cardiomyocyte growth and foetal gene expression occur as independent processes.


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CRRD Object Information
CRRD ID: 12792940
Created: 2017-03-16
Species: All species
Last Modified: 2017-03-16
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.