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To the Editor: Blanco-Colio et l1 showed that a fat-enriched breakfast increased the activation of the transcription factor nuclear factor-κB in peripheral blood mononuclear cells of normal subjects, an effect prevented by antioxidants present in red wine. We compared the effects of a high-fat meal and a high-carbohydrate meal (pizza), with or without dietary antioxidants, on the levels of soluble intercellular adhesion molecule-1 (sICAM-1) and vascular adhesion molecule-1 (sVCAM-1) in normal subjects. The genes of adhesion molecules are regulated by nuclear factor-κB,2 and circulating adhesion molecules are considered a molecular marker of early atherosclerosis.3 We studied 25 healthy non-obese volunteers (13 men and 12 women) aged 27±5.3 years (mean±SD). Subjects ate the following meals in random order and separated by a 1-week interval: (1) a high-fat meal (760 kcal; 50 g of fat, 20.4 g of saturated fat, 58 g of carbohydrates); (2) an isoenergetic high-carbohydrate (pizza) meal (758 kcal; 17 g of fat, 2.2 g …

Background Acute hyperglycemia may increase vascular tone in normal humans via a glutathione-sensitive, presumably free radical–mediated pathway. The objective of this study was to investigate whether or not the vascular effects of hyperglycemia are related to reduced availability of nitric oxide. Methods and Results Acute hyperglycemia (15 mmol/L, 270 mg/dL) was induced in 12 healthy subjects with an artificial pancreas. Systolic and diastolic blood pressures, heart rate, and plasma catecholamines showed significant increases ( P P P l -arginine (n=7, 1 g/min) but not d -arginine (n=5, 1 g/min) or l -lysine (n=5, 1 g/min) in the last 30 minutes of the hyperglycemic clamp completely reversed all hemodynamic and rheological changes brought about by hyperglycemia. Infusion of N G -monomethyl- l -arginine (L-NMMA; 2 mg/min) to inhibit endogenous nitric oxide synthesis in 8 normal subjects produced vascular effects qualitatively similar to those of hyperglycemia but quantitatively higher ( P Conclusions The results show that acute hyperglycemia in normal subjects causes significant hemodynamic and rheological changes that are reversed by l -arginine. Moreover, the effects of hyperglycemia are mimicked to a large extent, but not entirely, by infusion of L-NMMA. This suggests that hyperglycemia may reduce nitric oxide availability in humans.