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


METHODS
Forearm blood flow (FBF) was determined in 12 young healthy males with venous occlusion plethysmography.


RESULTS
Intra-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.


CONCLUSIONS
ET-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.
Böhm
Felix
F
Department of Cardiology, Karolinska University Hospital, Solna, S-171 76 Stockholm, Sweden. felix.bohm@ki.se
Settergren
Magnus
M
Pernow
John
J
D000109:Acetylcholine / Q000494:pharmacology; D000328:Adult; D001205:Ascorbic Acid / Q000494:pharmacology*; D001783:Blood Flow Velocity / Q000187:drug effects* / Q000502:physiology; D019332:Endothelin-1 / Q000502:physiology*; D005542:Forearm / Q000098:blood supply; D006801:Humans; D015850:Interleukin-6 / Q000097:blood / Q000378:metabolism*; D008297:Male; D009599:Nitroprusside / Q000494:pharmacology; D012016:Reference Values; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*; D000093242:Interleukin-6 Inhibitors
D000109:Acetylcholine; D001205:Ascorbic Acid; D019332:Endothelin-1; D015850:Interleukin-6; D009599:Nitroprusside; D000093242:Interleukin-6 Inhibitors