Ascorbate restores endothelium-dependent vasodilation impaired by acute hyperglycemia in humans.
BACKGROUND
Endothelium-dependent vasodilation is impaired in patients with insulin-dependent and non-insulin-dependent diabetes mellitus and restored by vitamin C administration, implicating a causative role for oxidant stress. Hyperglycemia per se attenuates endothelium-dependent vasodilation in healthy subjects. Accordingly, this study investigated whether impaired endothelium-dependent vasodilation caused by hyperglycemia in nondiabetic humans is restored by administration of the antioxidant vitamin C.


RESULTS
Endothelium-dependent vasodilation was measured by incremental brachial artery administration of methacholine chloride (0.3 to 10 microg/min) during euglycemia, after 6 hours of hyperglycemia (300 mg/dL) created by dextrose (50%) intra-arterial infusion, and with coadministration of vitamin C (24 mg/min) during hyperglycemia. Endothelium-dependent vasodilation was significantly diminished by hyperglycemia (P:=0.02 by ANOVA) and restored by vitamin C (P:=0.04). In contrast, endothelium-dependent vasodilation was not affected by equimolar infusions of mannitol, with and without vitamin C coinfusion (P:=NS). Endothelium-independent vasodilation was measured by incremental infusion of verapamil chloride (10 to 300 microg/min) without and with coadministration of N:(G)-monomethyl-L-arginine (L-NMMA). In the absence of L-NMMA, endothelium-independent vasodilation was not significantly altered during hyperglycemia (P:=NS) but was augmented by vitamin C (P:=0.04). The coadministration of L-NMMA eliminated the vitamin C-related augmentation in verapamil-mediated vasodilation.


CONCLUSIONS
Vitamin C administration restores endothelium-dependent vasodilation impaired by acute hyperglycemia in healthy humans in vivo. These findings suggest that hyperglycemia may contribute in part to impaired vascular function through production of superoxide anion.
Beckman
J A
JA
Cardiovascular Division, Brigham and Women's Hospital, Boston, MA 02115, USA.
Goldfine
A B
AB
Gordon
M B
MB
Creager
M A
MA
D000208:Acute Disease; D000328:Adult; D001205:Ascorbic Acid / Q000008:administration & dosage* / Q000378:metabolism; D001783:Blood Flow Velocity / Q000187:drug effects; D001786:Blood Glucose; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D005542:Forearm / Q000098:blood supply; D005947:Glucose / Q000008:administration & dosage; D015309:Glucose Clamp Technique; D006439:Hemodynamics; D006801:Humans; D006943:Hyperglycemia / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology*; D007261:Infusions, Intra-Arterial; D008297:Male; D016210:Methacholine Chloride / Q000008:administration & dosage; D009569:Nitric Oxide / Q000378:metabolism / Q000494:pharmacology; D009994:Osmolar Concentration; D014664:Vasodilation / Q000187:drug effects*; D014700:Verapamil / Q000494:pharmacology
D001786:Blood Glucose; D016210:Methacholine Chloride; D009569:Nitric Oxide; D014700:Verapamil; D005947:Glucose; D001205:Ascorbic Acid