Inhibitory effects of propofol on acetylcholine-induced, endothelium-dependent relaxation and prostacyclin synthesis in rabbit mesenteric resistance arteries

Background: Propofol (2,6-diisopropylphenol) modulates endothelium-dependen t relaxation in some arterial preparations. The effect of propofol on endot helium-dependent, prostacyclin-mediated responses in mesenteric resistance arteries has not yet been clarified. Methods: The effect of propofol was examined on acetylcholine-induced membr ane potential changes in the presence of NG-nitro-L-arginine (L-NOARG) in e ndothelium-intact rabbit mesenteric resistance arteries in vitro. The effec ts of propofol were also examined on the endothelium-dependent relaxation a nd prostacyclin synthesis that was induced by acetylcholine in the presence of L-NOARG and nicardipine, The effect of propofol on the relaxation induc ed by a prostacyclin analogue was examined in strips treated with L-NOARG a nd diclofenac, Results: Acetylcholine produced an initial and a slow membrane hyperpolariz ation, Propofol, 10 mu M, and diclofenac each inhibited the acetylcholine-i nduced slow hyperpolarization, but not the initial hyperpolarization. Acety lcholine produced an endothelium-dependent relaxation that was significantl y inhibited by propofol, 10 mu M, and diclofenac, Propofol, 10 mu M, greatl y inhibited the acetylcholine-induced synthesis of prostacyclin, as did dic lofenac, Propofol, 10 mu M, had no effect on the relaxation induced by a pr ostacyclin analog, Conclusions: In rabbit mesenteric resistance arteries, propofol inhibits th e synthesis of prostacyclin and thus attenuates acetylcholine-induced, endo thelium dependent responses. Our results may help to explain why some actio ns seen with propofol in some preparations (e.g., vasoconstriction) are not seen after the endothelium is removed.