The inhibition of aortic smooth muscle cell proliferation by the intravenous anesthetic ketamine.
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 [(3)H]thymidine incorporation and decreased the number of SMCs in a concentration-dependent manner (10-200 microM); neither propofol nor fentanyl inhibited [(3)H]thymidine incorporation into human aortic SMCs. The protein kinase C (PKC) inhibitor GF109203x abolished the ketamine-induced inhibition of [(3)H]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.
Shiga
Yousuke
Y
*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.
Minami
Kouichiro
K
Segawa
Kayoko
K
Uezono
Yasuhito
Y
Shiraishi
Munehiro
M
Sata
Takeyoshi
T
Yamamoto
Chieko
C
Sung-Teh
Kim
K
D000778:Anesthetics, Dissociative / Q000494:pharmacology*; D018686:Anesthetics, Intravenous; D000818:Animals; D001011:Aorta / Q000033:anatomy & histology / Q000166:cytology / Q000187:drug effects; D002404:Catheterization; D002452:Cell Count; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D017868:Cyclic AMP-Dependent Protein Kinases / Q000009:adverse effects; D017869:Cyclic GMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005283:Fentanyl / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D007649:Ketamine / Q000494:pharmacology*; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000187:drug effects*; D015742:Propofol / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D051381:Rats; D013936:Thymidine / Q000378:metabolism; D017539:Tunica Intima / Q000187:drug effects / Q000648:ultrastructure
D000778:Anesthetics, Dissociative; D018686:Anesthetics, Intravenous; D004791:Enzyme Inhibitors; D007649:Ketamine; D017868:Cyclic AMP-Dependent Protein Kinases; D017869:Cyclic GMP-Dependent Protein Kinases; D011493:Protein Kinase C; D005283:Fentanyl; D013936:Thymidine; D015742:Propofol