title: Propofol produces endothelium-independent vasodilation and may act as a Ca2+ channel blocker.
abstract: 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+.
authors.affiliation: Department of Anesthesiology, Oregon Health Sciences University, Portland 97201.
authors.forename: K S
authors.initials: KS
authors.lastname: Chang
authors.forename: R F
authors.initials: RF
authors.lastname: Davis
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D004347:Drug Interactions; D004730:Endothelium, Vascular / Q000187:drug effects*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D010656:Phenylephrine / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D015742:Propofol / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014664:Vasodilation / Q000187:drug effects*
chemical_list: D010656:Phenylephrine; D011189:Potassium Chloride; D002118:Calcium; D015742:Propofol