Vitamin C blocks vascular dysfunction and release of interleukin-6 induced by endothelin-1 in humans in vivo

ObjectiveInflammation of the vessel wall is of importance in atherosclerosis. Endothelin-1 (ET-1) exerts pro-inflammatory effects and contributes to endothelial dysfunction. The objective was to test whether ET-1 impairs vascular function by increasing oxidative stress and release of pro-inflammatory cytokines in humans.MethodsForearm blood flow (FBF) was determined in 12 young healthy males with venous occlusion plethysmography.ResultsIntra-brachial infusion of ET-1 (20 pmol/min) decreased both endothelium-dependent and -independent vasodilatation (P < 0.001). ET-1 also increased venous IL-6 levels (0.96 ± 0.14–1.40 ± 0.15 ng/ml; P < 0.001). Administration of Vitamin C (24 mg/min) following the ET-1 infusion did not restore vascular function. However, pre-treatment with Vitamin C before ET-1 prevented the decrease in endothelium-dependent and -independent vasodilatation as well as the increase in IL-6 levels (1.20 ± 0.28 versus 1.29 ± 0.27 ng/ml; P = 0.57). Infusion of a control vasoconstrictor substance, noradrenaline (80 ng/min) for 30 min did not affect IL-6 levels.ConclusionsET-1 impairs endothelium-dependent and -independent vasodilatation and stimulates release of IL-6 in humans in vivo. These effects are inhibited by pre-treatment with the antioxidant Vitamin C. This suggests that the mechanism by which ET-1 impairs vascular function and stimulates release of IL-6 involves increased oxidative stress.