Adenosine A1 receptor activation attenuates cardiac hypertrophy and fibrosis in response to α1-adrenoceptor stimulation in vivo
The research paper is based on the properties of the different adenosine receptors in the heart. The general property of adenosine as an anti-hypertrophic is recognized but the properties of the receptors on hypertrophic signaling in both in vitro and in vivo are unclear. The article focuses on the subtype Adenosine A1 characteristics. As the studies were conducted on 3-4 day old neonatal Sprague Dawley rats and mice, therefore, the European directive on laboratory animals (2010/63/EU) standards was maintained in the study. The lowest viable concentration of phenylephrine, angiotensin II (AngII) and insulin-like growth factor 1 (IGF1) were used in order to induce hypertrophic response in the hearts of the decapitated rats that were excised in a sterile environment in the cell culture studies. VisualSonicsVevo® 770 imaging system was used to conduct the echocardiography tests. For the MRI a horizontal bore 9.4 T MRI animal scanner was used. Tissue sampling, western blot analysis, and Histological analysis were also used. The up-regulation of the hypertrophic markers was higher in the case of the phenylephrine when compared to AngII. The stimulation of the α1-Adrenoceptor was used to upregulate the adenosine A1 receptors. In the case of phenylephrine-induced fibrosis the adenosine A1 receptors showed clear cardioprotective effects in the study. However, in the case of AngII and IGF1 the results were negative. Therefore, the evidence suggests the presence of a negative feedback mechanism that is related to the α1- adrenoceptor stimulation. Therefore the adenosine A1 receptors can be used as a target for therapy for the prevention of decompensated heart failure due to cardiac pressure. Therefore, the findings indicate a positive relationship between the phenylephrine administrations increasing the responsiveness of the adenosine A1 receptors. This is an effective countermeasure for α1- adrenoceptor-induced cardiomyocyte hypertrophy.
Source
Puhl, S. L., Kazakov, A., Müller, A., Fries, P., Wagner, D. R., Böhm, M., ... & Devaux, Y. (2016). Adenosine A1 receptor activation attenuates cardiac hypertrophy and fibrosis in response to α1‐adrenoceptor stimulation in vivo. British journal of pharmacology, 173(1), 88-102.
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