Antioxidant Vitamin C Improves Endothelial Dysfunction in Chronic Smokers

BACKGROUND: Chronic smoking is associated with endothelial dysfunction, an early stage of atherosclerosis. It has been suggested that endothelial dysfunction may be a consequence of enhanced degradation of nitric oxide secondary to formation of oxygen-derived free radicals. To test this hypothesis, we investigated the effects of the antioxidant vitamin C on endothelium-dependent responses in chronic smokers. METHODS AND RESULTS: Forearm blood flow responses to the endothelium-dependent vasodilator acetylcholine (7.5, 15, 30, and 60 micrograms/min) and the endothelium-independent vasodilator sodium nitroprusside (1, 3, and 10 micrograms/min) were measured by venous occlusion plethysmography in 10 control subjects and 10 chronic smokers. Drugs were infused into the brachial artery, and forearm blood flow was measured for each drug before and during concomitant intra-arterial infusion of the antioxidant vitamin C (18 mg/min). In control subjects, vitamin C had no effect on forearm blood flow in response to acetylcholine and sodium nitroprusside. In contrast, in chronic smokers the attenuated forearm blood flow responses to acetylcholine were markedly improved by concomitant administration of vitamin C, whereas the vasodilator responses to sodium nitroprusside were not affected. CONCLUSIONS: The present studies demonstrate that the antioxidant vitamin C markedly improves endothelium-dependent responses in chronic smokers. This observation supports the concept that endothelial dysfunction in chronic smokers is at least in part mediated by enhanced formation of oxygen-derived free radicals.