KETAMINE SUPPRESSES THE PRODUCTION AND RELEASE OF ENDOTHELIN-1 FROM CULTURED BOVINE ENDOTHELIAL-CELLS

Endothelins play important roles in the regulation of vascular tone. W e examined the effect of ketamine on the secretion of endothelin 1 (ET -1) and its precursor, ''big'' ET-1, from bovine carotid artery endoth elial cells (BCAECs). After confluent BCAEC cultures were incubated fo r 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 an d secreted ET-1 into the culture medium. The exposure of BCAECs to ket amine 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 mu M 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, there fore, the level of mature ET-1 in vascular endothelial cells. Implicat ions: Endothelins are important in the regulation of vascular tone. Th e effect of anesthetics on the production of endothelins is unknown. W e examined the effect of an anesthetic agent, ketamine, on the product ion and secretion of endothelin 1 from cultured vascular endothelial c ells and found that ketamine suppressed them.