Vitamin C improves resistance but not conduit artery endothelial function in patients with chronic renal failure.
BACKGROUND
Chronic renal failure is associated with impaired endothelium-dependent vasodilation and accelerated atherogenesis. To examine whether endogenous reactive oxygen species (ROS) modify endothelial function in renal failure, we evaluated the effect of the antioxidant vitamin C on endothelium-dependent responses in both the conduit and resistance vasculature of subjects with severe renal impairment.


METHODS
Endothelial function of the forearm resistance vasculature was assessed using plethysmography to measure the dilator response to intra-arterial acetylcholine (Ach) (25 to 100 nmol/min). Endothelial function of radial and brachial arteries was assessed using vascular ultrasound to measure the dilator response to flow during reactive hyperemia [flow-mediated dilatation (FMD)]. Studies were performed before and after administration of vitamin C by intra-arterial infusion (25 mg/min) in 33 predialysis patients or by intravenous infusion (3 g) in 17 hemodialysis patients.


RESULTS
Parenteral administration of vitamin C resulted in a 100-fold increase (intra-arterial studies) and a 4.5-fold increase (intravenous studies) in serum antioxidant activity. Vitamin C administration increased the dilator response to ACh in resistance vessels (P = 0.01), but did not alter the dilator response to flow in conduit vessels of either dialysis (P = 0.3) or predialysis subjects (P = 0.8). In the presence of the nitric oxide (NO) synthase inhibitor NGmonomethyl-L-arginine (L-NMMA), there was no effect of vitamin C on resistance vessel endothelial function. In all cases the dilator response to the endothelium-independent dilators was unaffected by vitamin C.


CONCLUSIONS
Acute administration of vitamin C reduces oxidant stress in renal failure and improves NO-mediated resistance vessel dilatation.
Cross
Jenny M
JM
Centre for Clinical Pharmacology & Therapeutics, Department of Medicine, University College London, England, United Kingdom. jenny.cross@clara.net
Donald
Ann E
AE
Nuttall
Sarah L
SL
Deanfield
John E
JE
Woolfson
Robin G
RG
Macallister
Raymond J
RJ
D000328:Adult; D000975:Antioxidants / Q000008:administration & dosage*; D001205:Ascorbic Acid / Q000008:administration & dosage*; D015415:Biomarkers; D001916:Brachial Artery / Q000502:physiology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology*; D005260:Female; D006801:Humans; D007676:Kidney Failure, Chronic / Q000188:drug therapy* / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D017534:Radial Artery / Q000502:physiology; D006435:Renal Dialysis; D014655:Vascular Resistance / Q000187:drug effects*; D014664:Vasodilation / Q000187:drug effects
D000975:Antioxidants; D015415:Biomarkers; D009569:Nitric Oxide; D001205:Ascorbic Acid