Suppression of endothelin-3-induced nitric oxide synthesis by triglyceride in human endothelial cells

Reduced endothelium-derived nitric oxide (NO) production characterizes several vascular diseases. This study examined the effect of triglyceride on NO production induced by endothelin-3 (ET-3) in cultured human umbilical vein endothelial cells. Triglyceride-rich human plasma obtained after a high-carbohydrate diet with white wine was used in an ex vivo study. The plasma triglyceride fraction was found to consist of large amounts of palmitic and oleic acids detected by gas-liquid chromatography. Therefore, the effect of synthetic tripalmitin and triolein emulsion on NO production was also examined. ET-3 stimulated NO and guanosine 3',5'-cyclic monophosphate production and increased cytosolic Ca2+ levels in the endothelial cells (ECs). After incubation of the ECs with the triglyceride-rich plasma for 2 h, these responses to ET-3 were ameliorated in a triglyceride concentration-dependent manner (50-200 mg/dl). A synthesized emulsion of tripalmitin (100 mg/dl) and triolein (100 mg/dl) also blunted the responses to ET-3. Neither endothelial constitutive NO synthase mRNA expression nor its protein level was affected by treatment with triglycerides. These results suggest that triglyceride suppresses ET-3-induced NO synthesis in human ECs by inhibiting cytosolic Ca2+ elevation.