Endothelium-dependent vasodilation is impaired in humans with diabetes mellitus. Inactivation of endothelium-derived nitric oxide by oxygen-derived free radicals contributes to abnormal vascular reactivity in experimental models of diabetes. To determine whether this observation is relevant to humans, we tested the hypothesis that the antioxidant, vitamin C, could improve endothelium-dependent vasodilation in forearm resistance vessels of patients with non-insulin-dependent diabetes mellitus. We studied 10 diabetic subjects and 10 age-matched, nondiabetic control subjects. Forearm blood flow was determined by venous occlusion plethysmography. Endothelium-dependent vasodilation was assessed by intraarterial infusion of methacholine (0.3-10 micrograms/min). Endothelium-independent vasodilation was measured by intraarterial infusion of nitroprusside (0.3-10 micrograms/min) and verapamil (10-300 micrograms/min). Forearm blood flow dose-response curves were determined for each drug before and during concomitant intraarterial administration of vitamin C (24 mg/min). In diabetic subjects, endothelium-dependent vasodilation to methacholine was augmented by simultaneous infusion of vitamin C (P = 0.002); in contrast, endothelium-independent vasodilation to nitroprusside and to verapamil were not affected by concomitant infusion of vitamin C (P = 0.9 and P = 0.4, respectively). In nondiabetic subjects, vitamin C administration did not alter endothelium-dependent vasodilation (P = 0.8). We conclude that endothelial dysfunction in forearm resistance vessels of patients with non-insulin-dependent diabetes mellitus can be improved by administration of the antioxidant, vitamin C. These findings support the hypothesis that nitric oxide inactivation by oxygen-derived free radicals contributes to abnormal vascular reactivity in diabetes.

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Vitamin C improves endothelium-dependent vasodilation in patients with non-insulin-dependent diabetes mellitus.

Background Endothelium-dependent vasodilation is impaired in humans with hypercholesterolemia. Oxidative degradation of endothelium-derived nitric oxide plays a major role in endothelial dysfunction in animal models of hypercholesterolemia. To assess whether this mechanism is relevant to humans, we studied the effect of vitamin C, an antioxidant, on vasodilator function in forearm resistance vessels of patients with hypercholesterolemia. Methods and Results We studied 11 hypercholesterolemic and 12 healthy control subjects. Forearm blood flow was determined by venous occlusion plethysmography. Endothelium-dependent vasodilation was assessed by intra-arterial infusion of methacholine (0.3 to 10 μg/min). Endothelium-independent vasodilation was measured by intra-arterial infusion of nitroprusside (0.3 to 10 μg/min) and verapamil (10 to 300 μg/min). Forearm blood flow dose-response curves were determined for each drug before and during coadministration of vitamin C (24 mg/min). In hypercholesterolemic subjec...

Vitamin C Improves Endothelium-Dependent Vasodilation in Forearm Resistance Vessels of Humans With Hypercholesterolemia

Pollen exposure induces allergic airway inflammation in sensitized subjects. The role of antigenic pollen proteins in the induction of allergic airway inflammation is well characterized, but the contribution of other constituents in pollen grains to this process is unknown. Here we show that pollen grains and their extracts contain intrinsic NADPH oxidases. The pollen NADPH oxidases rapidly increased the levels of ROS in lung epithelium as well as the amount of oxidized glutathione (GSSG) and 4-hydroxynonenal (4-HNE) in airway-lining fluid. These oxidases, as well as products of oxidative stress (such as GSSG and 4-HNE) generated by these enzymes, induced neutrophil recruitment to the airways independent of the adaptive immune response. Removal of pollen NADPH oxidase activity from the challenge material reduced antigen-induced allergic airway inflammation, the number of mucin-containing cells in airway epithelium, and antigen-specific IgE levels in sensitized mice. Furthermore, challenge with Amb a 1, the major antigen in ragweed pollen extract that does not possess NADPH oxidase activity, induced low-grade allergic airway inflammation. Addition of GSSG or 4-HNE to Amb a 1 challenge material boosted allergic airway inflammation. We propose that oxidative stress generated by pollen NADPH oxidases (signal 1) augments allergic airway inflammation induced by pollen antigen (signal 2).

https://dm5migu4zj3pb.cloudfront.net/manuscripts/24000/24422/JCI0524422.pdf

ROS generated by pollen NADPH oxidase provide a signal that augments antigen-induced allergic airway inflammation

Publisher Summary This chapter summarizes the basic science behind the hypothesis that antioxidants that might prevent cardiovascular disease (CVD). It reviews the observational epidemiology that relates to this hypothesis, and discusses the results of randomized trials examining primary and secondary prevention of CVD through dietary supplementation. The risks and benefits of various aspects of diet are likely to accrue over years or even decades, and eating habits change over time. Studies of diet and chronic disease may have to continue for many years and be updated periodically. Quantitative assessment of diet is based on self-reports, which results in misclassification. Dietary habits tend to be imbedded in cultural practices and associated with lifestyle factors, making it difficult to separate the effects of diet from other related factors on a given disease. One of the most consistent findings in dietary research is that those who consume higher amounts of fruits and vegetables have lower rates of cancer, heart disease, and stroke. Possible explanations for these apparent protective effects include higher dietary fiber intake, the replacement of fats and cholesterol, or specific micronutrients in fruits and vegetables, particularly those with antioxidant properties.

Dietary Antioxidants and Cardiovascular Disease

Dietary vitamin C supplementation reduces noise-induced hearing loss in guinea pigs

The second order rate constant for the reaction between ascorbic acid and superoxide at pH 7.4 using the xanthine-xanthine oxidase system was estimated to be 5.4 x 10(6) M-1 sec-1. The results indicate that the efficacies of superoxide dismutase and ascorbic acid for catalyzing the decay of superoxide radical in animal tissues are similar. The significance of ascorbic acid as a scavenger of superoxide is discussed from the point of view of evolution of ascorbic acid synthesizing capacity in the terrestrial vertebrates.

C Raha

Papers

Ascorbic acid: a scavenger of superoxide radical.