VASCULAR EFFECTS OF ACUTE HYPERGLYCEMIA IN HUMANS ARE REVERSED BY L-ARGININE - EVIDENCE FOR REDUCED AVAILABILITY OF NITRIC-OXIDE DURING HYPERGLYCEMIA

Background Acute hyperglycemia may increase vascular tone in normal hu mans via a glutathione-sensitive, presumably free radical-mediated pat hway. The objective of this study was to investigate whether or not th e vascular effects of hyperglycemia are related to reduced availabilit y of nitric oxide. Methods and Results Acute hyperglycemia (15 mmol/L, 270 mg/dL) was induced in 12 healthy subjects with an artificial panc reas. Systolic and diastolic blood pressures, heart rate, and plasma c atecholamines showed significant increases (P<.05) starting after 30 m inutes of hyperglycemia; leg blood flow decreased significantly (15%; P<.05) at 60 and 90 minutes. Platelet aggregation to ADP and blood vis cosity also showed significant increments (P<.05). The infusion of L-a rginine (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 comple tely reversed all hemodynamic and rheological changes brought about by hyperglycemia. Infusion of N-G-monomethyl-L-arginine (L-NMMA; 2 mg/mi n) to inhibit endogenous nitric oxide synthesis in 8 normal subjects p roduced vascular effects qualitatively similar to those of hyperglycem ia but quantitatively ly higher (P<.05); however, heart rate and plasm a catecholamine levels decreased during L-NMMA infusion, presumably as a consequence of baroreflex activation. Infusion of L-NMMA during hyp erglycemia produced changes not different from those obtained during i nfusion of L-NMMA alone. Conclusions The results show that acute hyper glycemia in normal subjects causes significant hemodynamic and rheolog ical changes that are reversed by L-arginine. Moreover, the effects of hyperglycemia are mimicked to a large extent, but nor entirely, by in fusion of L-NMMA. This suggests that hyperglycemia may reduce nitric o xide availability in humans.