Propofol prevents endothelial dysfunction induced by glucose overload

1. Surgical operations often induce acute hyperglycemia, which is known to affect endothelial functions. In this study, we examined the effects of propofol, a commonly used general anaesthetic, on bovine aortic endothelial cell (BAEC) dysfunction induced by glucose overload. 2. D-glucose overload (23 mM) induced an accumulation of superoxide anion (O₂^-), assessed by MCLA chemiluminescence, to a similar extent as that generated by 233 μU ml^-1 xanthine oxidase (XO) and 100 μM xanthine. Propofol inhibited this accumulation with an IC₅₀ of 0.21 μM, whereas much higher concentrations of propofol were required to scavenge O₂^- generated by 250 μU ml^-1 XO and 100 μM xanthine (IC₅₀: 13.5 μM). 3. D-glucose overload attenuated ATP-induced NO production which was detected using diaminofluorescence-2 (DAF-2). The inhibition was reversed by propofol with an EC₅₀ of 0.60 μM. In contrast, inhibitions caused by xanthine/XO were not altered by propofol (1 μM). 4. D-glucose overload suppressed ATP-induced Ca²⁺ oscillations and capacitative Ca²⁺ entry (CCE), which were both restored by superoxide dismutase, indicating that O₂^- was responsible. Propofol restored these attenuated Ca²⁺ oscillations and CCE with EC₅₀ of 0.31 and 1.0 μM, respectively. 5. D-glucose overload (23 mM) increased the intracellular glucose concentration 4 fold, compared with cells exposed to 5.75 mM glucose, and 1 μM propofol reduced this increase to 2.8 fold. 6. We conclude from these results that anaesthetic concentrations of propofol prevent the impairment of Ca²⁺-dependent NO production in BAEC induced by glucose overload. This effect is mainly due to the reduction of O₂^- accumulation, and involves, at least in part, the inhibition of cellular glucose uptake.