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October 17, 2009
9:00 AM - 11:00 AM
Room Area E
Sevoflurane Inhibits the Increase in Statin-Induced Endothelial Nitric Oxide Synthase Expression
  **   Kazuaki Tange, M.D., Yasuyuki Tokinaga, M.D., Ph.D., Koji Ogawa, M.D., Ph.D., Yoshio Hatano, M.D., Ph.D.
Anesthesiology, Wakayama Medical University, Wakayama, Japan

3-Hydoxy-3-Methylglutaryl-CoA (HMG-CoA) reductase inhibitors, statins, are among the most widely used for not only lipid lowering effect but also pleiotoropic effect. Beneficial effects independent of lipid lowering effects include improvements in endothelial function that may be due to increase endothelial nitric oxide (NO) synthase (eNOS) expression and activity both in acute and in chronic administration. Recently, the growing evidence that statin therapy improves endothelial function supports the concept that these agents may reduce the incidence of cardiovascular events induced by surgical stress. According to recommendations for Statin Therapy of ACC/AHA 2007 Perioperative Guidelines, statins should be continued throughout the perioperative period in patients chronically taking statins (1). On the other hand, inhalation anesthetics are thought to inhibit endothelium-dependent relaxation. However, there is no direct data demonstrating whether sevoflurane modulates the protective effect of statins on endothelial function. Therefore, the purpose of this study is to investigate the effect of sevoflurane on eNOS expression in cultured aortic endothelial cells acutely treated with simvastatin.


With institutional approval, bovine aortic endothelial cells (BAECs), passages 5-6, were used for experiments. eNOS expression level was examined by Western blotting using anti-eNOS antibody. Cells were exposed to 10 -7 M or 10 -6 M simvastatin for 15min in the presence or absence of 3.4% sevoflurane.

Data was normalized by beta-actin expression level. Statistical analysis was performed using Kruskal-Wallis H test followed Newman-Keuls-type as a post hoc. A P value < 0.05 was considered statistically significant.


Exposure to simvastatin for 15 min induced increase in eNOS expression in BAECs in a concentration-dependent manner. Sevoflurane inhibit the increase in eNOS expression induced by simvastatin (P< 0.05, n= 6) (Figure). Sevoflurane did not affect eNOS expression in BAECs without treatment with simvastatin.


The current findings suggest that sevoflurane may impair protective effect on statin-induced endothelial function by inhibiting of the increase in eNOS expression.

Reference: (1) ACC/AHA 2007 Perioperative Guidelines: e206-8.[figure1]

From Proceedings of the 2009 Annual Meeting of the American Society Anesthesiologists.
Figure 1