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Sevoflurane reduces endothelium-dependent vasorelaxation: role of Superoxide anion and endothelin

Le sévoflurane réduit la vasorelaxation provenant de l’endothélium: le rôle de l’anion superoxyde et de l’endothéline

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Abstract

Purpose

There are several reports suggesting that volatile anesthetics alter vascular endothelial function. We analyzed the effect of sevoflurane, a fluorinated volatile anesthetic, on nitric oxide (NO)-dependent relaxation, evaluating the role of the endotheliumderived vasoconstrictor endothelin-1 (ET-1).

Methods

The experiments were performed in rat isolated aortic segments aerated in the absence and in the presence of sevoflurane (2%).

Results

Acetylcholine-induced relaxation was reduced in aortic segments aerated with sevoflurane. Sevoflurane failed to modify relaxatation in response to an exogenous NO donor, sodium nitroprusside. Superoxide dismutase, a scavenger of Superoxide anion, partially restored the impaired vasorelaxation induced by sevoflurane, an effect that was associated with the release of Superoxide anion. The presence of BQ-123, an antagonist of endothelin ETA-type receptors, normalized the vasorelaxing response to acetylcholine in the presence of sevoflurane. In addition, BQ-123 also reduced the ability of the sevoflurane-incubated vascular wall to release Superoxide anion.

Conclusions

Our results suggest that sevoflurane impairs the endothelium-dependent vasorelaxation but that the endotheliumindependent response remains intact. ET-1 and Superoxide anion are involved in the endothelial dysfunction induced by sevoflurane. Further studies are needed to associate the endothelial dysfunction related to sevoflurane shown herein and its reported preconditioning properties on the myocardium.

Résumé

Objectif

Certains articles suggèrent que les anesthésiques volatils modifient la fonction endothéliale vasculaire. Nous avons analysé l’effet du sévoflurane, un anesthésique volatil fluoré, sur la relaxation liée à l’oxyde nitrique (NO) en évaluant le rôle de l’endothéline-1 (ET-1) vasoconstrictrice d’origine endothéliale.

Méthode

Les expériences ont été réalisées sur des segments aortiques isolés de rat aérés en l’absence et en présence de sévoflurane à 2 %.

Résultats

La relaxation induite par l’acétylcholine a été réduite dans les segments aérés avec le sévoflurane. Le sévoflurane n’a pas modifié la relaxation en réponse à un donneur de NO exogène, le nitroprussiate de sodium. La superoxyde dismutase, un piégeur de l’anion superoxyde, a partiellement restauré la vasorelaxation modifiée induite par le sévoflurane, un effet qui est associé à la libération de l’anion superoxyde. La présence de BQ-123, un antagoniste des récepteurs de type endothéline ETA, a normalisé la réponse vasorelaxante à l’acétylcholine en présence du sévoflurane. Le BQ-123 a aussi réduit la capacité de la paroi vasculaire mise en incubation dans le sévoflurane à libérer l’anion superoxyde.

Conclusion

Nos résultats laissent croire que le sévoflurane affecte la vasorelaxation d’origine endothéliale mais que la réponse indépendante de l’endothélium demeure intacte. LET-1 et l’anion superoxyde sont impliqués dans le dérèglement endothélial induit par le sévoflurane. D’autres études seront nécessaires pour pouvoir associer le dérèglement endothélial relié au sévoflurane démontré ici et ses propriétés mentionnées de préconditionnement sur le myocarde.

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Correspondence to Juan Carlos de la Pinta.

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Arriero, M.M., Alameda, L.M., Lopez-Farré, A. et al. Sevoflurane reduces endothelium-dependent vasorelaxation: role of Superoxide anion and endothelin. Can J Anesth 49, 471–476 (2002). https://doi.org/10.1007/BF03017923

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Keywords

  • Sevoflurane
  • Aortic Ring
  • Volatile Anesthetic
  • Aortic Segment
  • Release Superoxide Anion