This study was undertaken to determine the direct actions of propofol, and whether propofol exerts any action on basal endothelium-derived relaxing factor release and vasodilator effect of acetylcholine on phenylephrine-induced contractile responses in isolated rat aortic rings. This compound is known to produce a fall in blood pressure in man and animals, and it has been suggested that the hypotension may result from a direct vasodilator action on the veins and arterioles. In this study, propofol did not induce any contractile response in aortic rings at various concentrations (10(-8)-10(-4) M). Propofol did not significantly alter phenylephrine-induced contractions at lower concentrations (10(-8)-10(-6) M) but at higher concentrations (10(-5)-10(-4) M) the depression caused by propofol was significant in both endothelium-intact and -denuded rings. Pretreatment of the endothelium-intact rings with propofol (10(-6) and 10(-5) M) produced a reduction in the relaxant effect of acetylcholine. The results obtained in this study demonstrate that clinically relevant concentrations of propofol (10(-6) M or less) have no direct vasodilator effects and that it reduces endothelium-dependent relaxation to acetylcholine.