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.
Cardiovascular Division, Brigham and Women's Hospital, Boston, MA 02115, USA.
J A
JA
Beckman
A B
AB
Goldfine
M B
MB
Gordon
M A
MA
Creager
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