AbstractActivation of beta2 adrenoceptors with salbutamol has been reported as cardio toxic. In this study, the investigation was to find out whether the beta2 agonist salbutamol protects the myocardium from ischemic reperfusion injury, when administered at reperfusion or post reperfusion.
Administration of beta2 agonist salbutamol (1nM) at the onset of reoxygenation significantly decreased the live cells. Moreover, the administration of salbutamol (1nM) in the presence of beta2-AR selective antagonist ICI 118,551 showed a significant decrease in the live cells through a cardio toxic manner. This study further showed that, beta2 agonist salbutamol in the presence of beta1-AR selective antagonist CGP 12177 decreased the live cell population.
Administration of beta2 agonist salbutamol (0.01nM) throughout the reperfusion injury also decreased the population of live cells. Also, the administration of salbutamol (0.01nM) with the beta2 antagonist ICI and beta1 antagonist CGP showed the decrease in live cells. Besides the administration of beta2 agonist salbutamol (1µM, 10nM, and 0.1nM) at the onset of reperfusion showed a significant increase in necrosis and the administration of beta2 agonist salbutamol (1nM) in the presence of beta2 antagonist ICI throughout the reperfusion injury exposed an increase in the necrosis.
Caspase-3 is an effector caspase. The activity of the Caspase-3 is monitored in this study to detect the apoptotic status of cell population. In this study, the intracellular staining of isolated rat myocytes with Alexa Fluor® 488 labelled caspase-3 antibodies were used. The flowcytometric analysis of caspase-3 activation in cells showed an increase in the caspase-3 level, especially with the administration of salbutamol 10nM and 0.1nM. Moreover, the administration of salbutamol (1nM, 0.1nM) in the presence and absence of β2 antagonist ICI and the β1 antagonist CGP showed a fold increase in the caspase level.
Collectively, this study demonstrated that, the administration of β2 agonist salbutamol at the onset of reperfusion will not protect the ischemic reperfused rat myocardium from the ischemic reperfusion injury. Besides, it causes a toxic effect in the cardiomyocyte with the increase of apoptotic and necrotic status of cell population. Also, the decrease in live cells population showed the cardio toxic effect of β2 agonist salbutamol.
|Date of Award||2011|
|Supervisor||Helan Merdek (Supervisor)|