This study investigated the effect of propofol on the pulmonary vascular bed of the rat. Propofol (5 x 10(-6) to 5 x 10(-4) M) did not alter the basal perfusion pressure in isolated rat lungs perfused at a constant flow (0.03 mL g body wt(-1) min(-1)) with Krebs-Henseleit solution. When perfusion pressure was elevated by raising the K+ concentration to 30 mM (depolarizing Krebs-Henseleit solution), propofol decreased it in a concentration-dependent manner. Indomethacin (3 x 10(-6) M) and N-G-nitro-L-arginine methyl ester (10(-4) M) did not affect the response to propofol, which excluded the role of cyclo-oxygenase metabolites and nitric oxide, respectively. The ATP-sensitive K+ (K-ATP(+)) channel blocker glibenclamide (3 x 10(-6) and 10(-5) M) inhibited the vasodilator effect of propofol. When lungs were perfused with Ca2+-free depolarizing Krebs-Henseieit solution, 0.1-2.5 mM Ca+2 produced a concentration-dependent presser response. Propofol (5 x 10(-5) M) attenuated the vasopressor response to Ca2+ significantly. In conclusion, the activation of K-ATP(+) channels is probably the major mechanism of the vasodilator effect of propofol, at clinically relevant concentrations, in the rat lung. The Ca2+ antagonistic property of propofol is evident only at higher concentrations.