Vitamin C prevents hyperoxia-mediated vasoconstriction and impairment of endothelium-dependent vasodilation

Abstract

. Vitamin C prevents hyperoxia-mediated vasoconstriction and impairment of endothelium-dependent vasodilation. Am J Physiol Heart Circ Physiol 282: H2414-H2421, 2002. First published January 10, 2002 10.1152/ajpheart.00947.2001.-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 endotheliumderived vasoactive factors.oxygen; acetylcholine; heart failure; endothelium HIGH ARTERIAL BLOOD OXYGEN (O 2 tension) causes vasoconstriction in healthy humans (2,4,6,7,28). Although hyperoxic vasoconstriction was first reported at least 90 years ago (2), the mechanism(s) for this phenomenon in healthy humans is poorly understood. Several animal models of hyperoxic vasoconstriction suggest that O 2 tension may influence one or more of the endothelium-derived factors that contribute to the maintenance of vascular tone, such as NO, endothelin, and vasoactive prostaglandins (5,26,29,35). One potential mechanism by which hyperoxia may affect these vasoactive substances is the generation of reactive oxygen species (ROS) that occurs with increased O 2 tension. For example, it has been demonstrated in vitro that superoxide anions derived from hyperoxia react rapidly with NO (37), thereby, decreasing its bioavailability. However, in healthy humans, the hypothesis that hyperoxic vasoconstriction is related to ROS generation or that hyperoxia may impair the function of endothelium-derived vasoactive factors has not b...

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