Effects of Beta-Adrenoceptors Overexpression on Cell Survival Are Mediated by Bax/Bcl-2 Pathway in Rat Cardiac Myocytes

Background: Chronic activation of β-adrenoceptors (β-ARs) results in cardiac myocyte injury, even death, and diminishes the number of β-ARs. Objectives: To investigate the effects of overexpression of β1- or β2-AR on cardiomyocytes injured by isoprenaline (ISO). Methods: We have used an adenoviral vector carrying the sequence for human β1- or β2-AR (Adv.β1, Adv.β2) to increase the content of β1 or β2-AR in isolated adult rat ventricular myocytes, and we have examined the cell survival and the expression of Bax and Bcl-2. Results: With use of adenoviral vectors, the β1- and β2-AR contents of myocytes were increased 2.98- and 2.87-fold, respectively. Overexpression of β1-AR sharpened the cellular injury of ISO. If β2-AR activity was further blocked by addition of selective β2-AR antagonist ICI118,551, the cells were more sensitive to the impairment of Adv.β1 + ISO. Overexpression of Adv.β2 partially inversed the cytotoxicity of ISO stimulation. The beneficial effects were strengthened by addition of CGP20712A, a β1-AR-blocking agent. Western blot analysis demonstrated that both increasing β1-AR and inhibition of β2-AR increased the ratio of Bax/Bcl-2. Whereas, increasing β2-AR and inhibition of β1-AR decreased the ratio of Bax/ Bcl-2. Control adenovirus CGP had no effect on cell survival. Conclusions: Overexpression of Adv.β2 and/or inhibition of β1-AR have protective effect on adult rat ventricular myocytes chronically stimulated by ISO. Overexpression of Adv.β1 and/or inhibition of β2-AR are deleterious in the same state. The effects of β-ARs on cell survival might be mediated by the Bax/Bcl-2 signal pathway.