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-dependent relaxation in some arterial preparations. The effect of propofol on endothelium-dependent, prostacyclin-mediated responses in mesenteric resistance arteries has not yet been clarified.


METHODS
The effect of propofol was examined on acetylcholine-induced membrane potential changes in the presence of N(G)-nitro-L-arginine (L-NOARG) in endothelium-intact rabbit mesenteric resistance arteries in vitro. The effects of propofol were also examined on the endothelium-dependent relaxation and prostacyclin synthesis that was induced by acetylcholine in the presence of L-NOARG and nicardipine. The effect of propofol on the relaxation induced by a prostacyclin analogue was examined in strips treated with L-NOARG and diclofenac.


RESULTS
Acetylcholine produced an initial and a slow membrane hyperpolarization. Propofol, 10 microM, and diclofenac each inhibited the acetylcholine-induced slow hyperpolarization, but not the initial hyperpolarization. Acetylcholine produced an endothelium-dependent relaxation that was significantly inhibited by propofol, 10 microM, and diclofenac. Propofol, 10 microM, greatly inhibited the acetylcholine-induced synthesis of prostacyclin, as did diclofenac. Propofol, 10 microM, had no effect on the relaxation induced by a prostacyclin analog.


CONCLUSIONS
In rabbit mesenteric resistance arteries, propofol inhibits the synthesis of prostacyclin and thus attenuates acetylcholine-induced, endothelium-dependent responses. Our results may help to explain why some actions seen with propofol in some preparations (e.g., vasoconstriction) are not seen after the endothelium is removed.
Yamashita
A
A
Department of Anesthesiology and Critical Care Medicine, Kagoshima University Faculty of Medicine, Japan.
Kajikuri
J
J
Ohashi
M
M
Kanmura
Y
Y
Itoh
T
T
D000109:Acetylcholine / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D018686:Anesthetics, Intravenous / Q000494:pharmacology; D000818:Animals; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D011464:Epoprostenol / Q000037:antagonists & inhibitors* / Q000096:biosynthesis*; D066298:In Vitro Techniques; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D009126:Muscle Relaxation / Q000187:drug effects* / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D015742:Propofol / Q000494:pharmacology*; D011817:Rabbits; D014655:Vascular Resistance / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology
D018686:Anesthetics, Intravenous; D014665:Vasodilator Agents; D011464:Epoprostenol; D000109:Acetylcholine; D015742:Propofol