Vitamin C prevents hyperoxia-mediated vasoconstriction and impairment of endothelium-dependent vasodilation.
High arterial blood oxygen tension increases vascular resistance, possibly related to an interaction between reactive oxygen species and endothelium-derived vasoactive factors. Vitamin C is a potent antioxidant capable of reversing endothelial dysfunction due to increased oxidant stress. We tested the hypotheses that hyperoxic vasoconstriction would be prevented by vitamin C, and that acetylcholine-mediated vasodilation would be blunted by hyperoxia and restored by vitamin C. Venous occlusion strain gauge plethysmography was used to measure forearm blood flow (FBF) in 11 healthy subjects and 15 congestive heart failure (CHF) patients, a population characterized by endothelial dysfunction and oxidative stress. The effect of hyperoxia on FBF and derived forearm vascular resistance (FVR) at rest and in response to intra-arterial acetylcholine was recorded. In both healthy subjects and CHF patients, hyperoxia-mediated increases in basal FVR were prevented by the coinfusion of vitamin C. In healthy subjects, hyperoxia impaired the acetylcholine-mediated increase in FBF, an effect also prevented by vitamin C. In contrast, hyperoxia had no effect on verapamil-mediated increases in FBF. In CHF patients, hyperoxia did not affect FBF responses to acetylcholine or verapamil. The addition of vitamin C during hyperoxia augmented FBF responses to acetylcholine. These results suggest that hyperoxic vasoconstriction is mediated by oxidative stress. Moreover, hyperoxia impairs acetylcholine-mediated vasodilation in the setting of intact endothelial function. These effects of hyperoxia are prevented by vitamin C, providing evidence that hyperoxia-derived free radicals impair the activity of endothelium-derived vasoactive factors.
Mak
Susanna
S
Cardiovascular Division, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, M5G 1X5 Canada.
Egri
Zoltan
Z
Tanna
Gemini
G
Colman
Rebecca
R
Newton
Gary E
GE
D000109:Acetylcholine / Q000494:pharmacology; D000328:Adult; D000975:Antioxidants / Q000494:pharmacology*; D001205:Ascorbic Acid / Q000494:pharmacology*; D001783:Blood Flow Velocity; D001794:Blood Pressure; D004730:Endothelium, Vascular / Q000502:physiology*; D005260:Female; D005542:Forearm / Q000098:blood supply; D006333:Heart Failure / Q000188:drug therapy / Q000503:physiopathology; D006339:Heart Rate; D006801:Humans; D018496:Hyperoxia / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress; D014655:Vascular Resistance; D014661:Vasoconstriction / Q000187:drug effects*; D014664:Vasodilation / Q000187:drug effects*; D014700:Verapamil / Q000494:pharmacology
D000975:Antioxidants; D014700:Verapamil; D000109:Acetylcholine; D001205:Ascorbic Acid