Previous Abstract | Next Abstract
Printable Version
October 14, 2014
1:00 PM - 3:00 PM
Room Hall B1-Area C
Desflurane as Well as Sevoflurane Inhibits Endothelium-dependent Vasodilation by a Different Mechanism
Satoshi Kazuma, M.D., Yasuyuki Tokinaga, M.D., Yukimasa Takada, M.D., Shunsuke Hayashi, none, Michiaki Yamakage, M.D., Ph.D.
Sapporo Medical University, Sapporo, Japan
Background: The physiological mechanisms that regulate tissue blood flow sufficiently to fulfill metabolic requirements are involved in the control of vascular tone. Nitric oxide, which is produced by endothelial nitric oxide synthase (eNOS), acts endothelium-dependent vasodilation. eNOS activity is regulated by several mechanisms including intracellular calcium concentration and phosphorylation of the threonine residue and serine residue of eNOS protein. Phosphorylation of Ser1177 increases Ca2+ sensitivity of the enzyme (1).

The effect of volatile anesthe6tics on control of vascular tone is complex and depends on the agonist and various vascular beds (2). Endothelium-dependent vasodilation is one of the controls of vascular tone and is impaired by sevoflurane (3). The interaction of desflurane locally with the action of endothelial cells of vessels remains unknown. This study was carried out to elucidate the effects of desflurane and sevoflurane on endothelium-dependent vasodilation and the mechanisms of regulation of eNOS activity.

Methods: With institutional approval, the rat descending aorta with the endothelium was suspended in a temperature-controlled organ bath for measurement of isometric tension. Changes in tension in response to phenylephrine (3×10-7 M) followed by acetylcholine (1×10-6 M) were recorded in the presence or absence of desflurane (5.7%, 11.4%; 1, 2 MAC for normal rats) or sevoflurane (2.4%, 4.8%; 1, 2 MAC for normal rats) to test endothelium-dependent vasodilation. To confirm the effects of anesthetics on endothelium-dependent vasodilation, endothelium-independent vasodilation was tested. Endothelium-denuded aorta smooth muscle was suspended in the organ bath, and changes in tension in response to phenylephrine (3×10-7 M) followed by sodium nitroprusside (1×10-5 M) were recorded prior to and after application of desflurane or sevoflurane.

Cultured bovine aortic endothelial cells were treated with bradykinin (1×10-6 M) in the presence or absence of desflurane or sevoflurane (11.4% and 4.8%, respectively). After treatments, Western blotting was used to determine eNOS-Ser1177 phosphorylation. Statistical analysis was performed using Kruskal-Wallis’ H-test followed by Newman-Keuls test for multiple comparisons. P value < 0.05 was considered statistically significant.

Results: Both desflurane and sevoflurane significantly inhibited endothelium-dependent vasodilation of the rat aorta (Figure 1A), whereas there was no inhibition of endothelium-independent vasodilation either of the anesthetics (data not shown). Western blotting revealed that phosphorylation of the Ser1177 site of the eNOS protein was inhibited by sevoflurane but not by desflurane (Figure 1B).

Conclusion: The findings suggest that sevoflurane inhibits endothelium-dependent vasodilation caused by inhibition of phosphorylation of the Ser1177 residue of the eNOS protein, whereas desflurane inhibits vasodilation by another regulation pathway of eNOS activity. The results of this study suggest that in a situation to preserve endothelial function, such as severe ischemic heart disease, desflurane and sevoflurane should be used cautiously.


(1) Förstermann U, et al., Eur Heart J 2012 ; 33 : 829-37 (2) Akata T. Anesthesiology 2007 ; 106 : 365-91. (3) Arriero MM, et al. Can J Anaesth 2002; 49: 471-6.
Figure 1

Copyright © 2014 American Society of Anesthesiologists