Propofol prevents endothelial dysfunction induced by glucose overload

Yuji Karashima, Masahiro Oike, Shosuke Takahashi, Yushi Ito

Research output: Contribution to journalArticlepeer-review

10 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)683-691
Number of pages9
JournalBritish Journal of Pharmacology
Volume137
Issue number5
DOIs
Publication statusPublished - Nov 2002
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Pharmacology

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