Propofol-induced alterations in myocardial beta-adrenoceptor binding and responsiveness

Propofol (iv) depresses cardiovascular function in both humans and animals. However, the mechanism underlying this action has not been well described. The present study was designed to test the hypothesis that this effect of propofol results in part from an antagonism of adrenergic control of the he art. Experiments examined effects of propofol on: 1) [H-3]CGP12177 (a beta- adrenoceptor antagonist) binding in rat myocardial membranes; and 2) the in otropic and chronotropic actions of isoproterenol in rat left atrial muscle and right atria, respectively. Propofol (25-200 mu M) increased the appare nt dissociation constant for [H-3]CGP12177 without affecting binding site d ensity. Similarly, 200 mu M propofol increased the 50% effective concentrat ion values for the dose-dependent positive chronotropic and inotropic actio ns of isoproterenol in right and left atria, and depressed the maximum incr ease in spontaneous rate elicited by this beta-adrenoceptor agonist. Other experiments demonstrated that propofol does not alter muscarinic receptor b inding as monitored using [H-3]quinuclidinylbenzilate. in conclusion, these results indicate that propofol can decrease cardiac beta-adrenoceptor resp onsiveness; however, the concentrations of propofol required suggest that t his action contributes to the cardiovascular depression produced by this an esthetic only during large-dose bolus injection. Implications: Experiments in membranes and cardiac preparations isolated from rat heart demonstrate t hat relatively high concentrations of propofol (25-200 mu M) are required t o antagonize beta-adrenoceptor binding and tissue responsiveness.