This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Shiga, Y. Articles by Sung-Teh, K. Search for Related Content PubMed PubMed Citation Articles by Shiga, Y. Articles by Sung-Teh, K. Related Collections Cardiovascular Mechanisms Pharmacology

---

ANESTHETIC PHARMACOLOGY

The Inhibition of Aortic Smooth Muscle Cell Proliferation by the Intravenous Anesthetic Ketamine

Yousuke Shiga, MD PhD^*, Kouichiro Minami, MD PhD^*, Kayoko Segawa, MD PhD, Yasuhito Uezono, MD PhD, Munehiro Shiraishi, MD^*, Takeyoshi Sata, MD PhD^*, Chieko Yamamoto, PhD, and Kim Sung-Teh, MD

*Department of Anesthesiology, University of Occupational and Environmental Health, Kitakyushu, Japan; Kitakyushu Institute of Biophysics, Fukuoka, Japan; and Department of Pharmacology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan

Address correspondence and reprint requests to K. Minami, MD PhD, Assistant Professor, Department of Anesthesiology, University of Occupational and Environmental Health School of Medicine, 1–1 Iseigaoka, Yahatanishiku, Kitakyushu 807–8555, Japan. Address email to kminami{at}med.uoeh-u.ac.jp

Smooth muscle cell (SMC) proliferation has been recognized as central to the pathology of both major forms of vascular disease, atherosclerosis and hypertension. Recently, we reported that ketamine inhibits rat mesangial cell proliferation, suggesting that ketamine inhibits cell growth. Although the IV anesthetic ketamine has been widely used clinically, the exact effects of ketamine on vascular SMC proliferation have not been studied. In this study, we investigated the effects of ketamine on vascular SMC proliferation. Ketamine inhibited [³H]thymidine incorporation and decreased the number of SMCs in a concentration-dependent manner (10–200 µM); neither propofol nor fentanyl inhibited [³H]thymidine incorporation into human aortic SMCs. The protein kinase C (PKC) inhibitor GF109203x abolished the ketamine-induced inhibition of [³H]thymidine incorporation into SMC, but the inhibition was not affected by either the protein kinase A inhibitor H-89 or the protein kinase G inhibitor KT5823. A histological analysis demonstrated the inhibitory effect of ketamine on the intimal thickening of the balloon-injured rat aorta. Based on these results, ketamine inhibits SMCs at clinical concentrations via the PKC pathway. Our results indicate that ketamine might prevent the proliferation of SMCs clinically.

IMPLICATIONS: Vascular smooth muscle cell (SMC) proliferation has been recognized as central to the pathology of major forms of vascular disease. Ketamine inhibited SMCs at clinical concentrations via the protein kinase C pathway. Our present results indicate that ketamine might prevent the proliferation of SMCs clinically.