(Circulation. 1997;95:1783-1790.)
© 1997 American Heart Association, Inc.
Articles |
Vascular Effects of Acute Hyperglycemia in Humans Are Reversed by L-Arginine
Evidence for Reduced Availability of Nitric Oxide During Hyperglycemia
From the Department of Geriatrics and Metabolic Diseases (D.G., R.M., L.C., G.V., R.A., R.G., F.N., F.D.) and Institute of Pharmacology and Toxicology (C.L.), Second University of Naples, Italy.
Correspondence to Prof D. Giugliano, MD, Via Emilia 1, 80021 Afragola (NA), Italy.
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<.05) starting after 30 minutes of hyperglycemia; leg blood flow decreased significantly (15%; P<.05) at 60 and 90 minutes. Platelet aggregation to ADP and blood viscosity also showed significant increments (P<.05). The infusion of 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 NG-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<.05); however, heart rate and plasma catecholamine levels decreased during L-NMMA infusion, presumably as a consequence of baroreflex activation. Infusion of L-NMMA during hyperglycemia produced changes not different from those obtained during infusion of L-NMMA alone.
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.
Key Words: hyperglycemia • hemodynamics • rheology • amino acids
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