Abstract
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 β<sub>1</sub>- or β<sub>2</sub>-AR on cardiomyocytes injured by isoprenaline (ISO). Methods: We have used an adenoviral vector carrying the sequence for human β<sub>1</sub>- or β<sub>2</sub>-AR (Adv.β<sub>1</sub>, Adv.β<sub>2</sub>) to increase the content of β<sub>1</sub> or β<sub>2</sub>-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 β<sub>1</sub>- and β<sub>2</sub>-AR contents of myocytes were increased 2.98- and 2.87-fold, respectively. Overexpression of β<sub>1</sub>-AR sharpened the cellular injury of ISO. If β<sub>2</sub>-AR activity was further blocked by addition of selective β<sub>2</sub>-AR antagonist ICI118,551, the cells were more sensitive to the impairment of Adv.β<sub>1</sub> + ISO. Overexpression of Adv.β<sub>2</sub> partially inversed the cytotoxicity of ISO stimulation. The beneficial effects were strengthened by addition of CGP20712A, a β<sub>1</sub>-AR-blocking agent. Western blot analysis demonstrated that both increasing β<sub>1</sub>-AR and inhibition of β<sub>2</sub>-AR increased the ratio of Bax/Bcl-2. Whereas, increasing β<sub>2</sub>-AR and inhibition of β<sub>1</sub>-AR decreased the ratio of Bax/ Bcl-2. Control adenovirus CGP had no effect on cell survival. Conclusions: Overexpression of Adv.β<sub>2</sub> and/or inhibition of β<sub>1</sub>-AR have protective effect on adult rat ventricular myocytes chronically stimulated by ISO. Overexpression of Adv.β<sub>1</sub> and/or inhibition of β<sub>2</sub>-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.
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