Ketamine suppresses the production and release of endothelin 1 from cultured bovine endothelial cells.
Endothelins play important roles in the regulation of vascular tone. We examined the effect of ketamine on the secretion of endothelin 1 (ET-1) and its precursor, "big" ET-1, from bovine carotid artery endothelial cells (BCAECs). After confluent BCAEC cultures were incubated for 24 h with various concentrations of ketamine, the antigen levels for both ET-1 and big ET-1 in the culture medium were determined by using sandwich enzyme-linked immunosorbent assays. The precursor protein ET-1 (preproET-1) mRNA levels were assessed by using Northern blotting. On incubation in fresh medium, the BCAECs time-dependently produced and secreted ET-1 into the culture medium. The exposure of BCAECs to ketamine dose-dependently decreased the secretion of ET-1 and big ET-1 in both the serum-free and serum-containing conditions. Approximately 40% inhibition was attained by treatment with 100 microM ketamine for 24 h. The mRNA encoding preproET-1 was expressed much more slowly and to a lesser extent in the presence of ketamine. These results suggest that ketamine suppresses the production and release of big ET-1 and, therefore, the level of mature ET-1 in vascular endothelial cells.


CONCLUSIONS
Endothelins are important in the regulation of vascular tone. The effect of anesthetics on the production of endothelins is unknown. We examined the effect of an anesthetic agent, ketamine, on the production and secretion of endothelin 1 from cultured vascular endothelial cells and found that ketamine suppressed them.
Shakunaga
K
K
Department of Anesthesiology, Faculty of Medicine, Toyama Medical and Pharmaceutical University, Japan. shaku@ms.toyama-mpu.ac.jp
Kojima
S
S
Jomura
K
K
Shimizu
Y
Y
Satone
T
T
Ito
Y
Y
D000778:Anesthetics, Dissociative / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002417:Cattle; D002478:Cells, Cultured; D019332:Endothelin-1 / Q000096:biosynthesis*; D016232:Endothelins / Q000235:genetics; D004730:Endothelium, Vascular / Q000378:metabolism*; D007649:Ketamine / Q000494:pharmacology*; D011498:Protein Precursors / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis
D000778:Anesthetics, Dissociative; D019332:Endothelin-1; D016232:Endothelins; D011498:Protein Precursors; D012333:RNA, Messenger; D007649:Ketamine; D002118:Calcium