Propofol produces endothelium-independent vasodilation and may act as a Ca2+ channel blocker.

The mechanism of vasodilation induced by propofol was investigated using isolated rat thoracic aortic rings. Aortic rings were precontracted with potassium chloride (KCl) (40 mM) or phenylephrine (PE) (3 x 10(-8) to 3 x 10(-7) M) in the presence and absence of intact endothelium. Propofol produced similar concentration-dependent relaxation in aortic rings with and without endothelium regardless of whether they were precontracted with KCl or PE. The relaxation response to propofol was significantly greater in KCl-contracted aortic rings than in PE-contracted aortic rings. The propofol concentration producing 50% relaxation from the contracted state (RC50) was lower in aortic rings contracted with KCl than with PE, both with (5 +/- 0.6 x 10(-5) M vs 8.3 +/- 5.7 x 10(-4) M, P < 0.001) and without intact endothelium (3.9 +/- 0.5 x 10(-5) M vs 7.2 +/- 3.8 x 10(-4) M, P < 0.001). Propofol inhibited the Ca(2+)-induced contractions of aortic rings exposed to Ca(2+)-free media and depolarized with KCl (40 mM, 100 mM) in a dose-dependent manner. These effects are similar to those produced by verapamil. Propofol (5 x 10(-5) M) had minimal effect on the intracellular Ca2+ release elicited by PE (10(-5) M). We conclude that vasodilation produced by propofol is not endothelium-dependent but is likely due to blockade of voltage-gated influx of extracellular Ca2+.