STIMULATION OF ENDOTHELIN-1 PRODUCTION BY THROMBIN, BUT LACK OF INTERFERENCE BY HIGH AMBIENT GLUCOSE IN-VITRO

Diabetic vascular disease is associated with a state of hypercoagulabi lity and altered endothelial properties, leading to elevated plasma le vels of endothelium-derived peptides and proteins, e.g. endothelin-1, von Willebrand factor or fibronectin. This study determined dynamic im munoreactive endothelin-1 secretion by human umbilical vein endothelia l cells exposed to thrombin (5 x 10(6) mU/l) in the presence (40 mmol/ l) and absence (5.5 mmol/l) of excessive glucose in the cell culture m edium. Exposure to high glucose and thrombin concentrations was initia ted after cell confluency and applied for 24 h for measurements of end othelin-1 and for 2 and 5 h for the determination of preproendothelin- 1, von Willebrand factor and fibronectin messenger ribonucleic acid. C omparisons were made versus cells incubated with normal glucose concen trations or with high mannose or NaCl concentrations as osmotic contro l. Neither preproendothelin-1, fibronectin and von Willebrand factor m essenger ribonucleic acid expression nor endothelin-1 release was affe cted by high concentrations of glucose, mannose or sodium chloride.