Document Detail


Vascular effects of acute hyperglycemia in humans are reversed by L-arginine. Evidence for reduced availability of nitric oxide during hyperglycemia.
MedLine Citation:
PMID:  9107164     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
D Giugliano; R Marfella; L Coppola; G Verrazzo; R Acampora; R Giunta; F Nappo; C Lucarelli; F D'Onofrio
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Circulation     Volume:  95     ISSN:  0009-7322     ISO Abbreviation:  Circulation     Publication Date:  1997 Apr 
Date Detail:
Created Date:  1997-05-13     Completed Date:  1997-05-13     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  0147763     Medline TA:  Circulation     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1783-90     Citation Subset:  AIM; IM    
Affiliation:
Department of Geriatrics and Metabolic Diseases, Second University of Naples, Italy.
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MeSH Terms
Descriptor/Qualifier:
Acute Disease
Adult
Arginine / pharmacology*
Blood Viscosity / drug effects
Catecholamines / blood
Female
Free Radicals
Glucose / diagnostic use
Glutathione / physiology
Hemodynamics / drug effects
Humans
Hyperglycemia / physiopathology*
Insulin / blood
Lysine / pharmacology
Male
Nitric Oxide / biosynthesis,  physiology*
Platelet Aggregation / drug effects
Vasoconstriction / drug effects*
omega-N-Methylarginine / pharmacology
Chemical
Reg. No./Substance:
0/Catecholamines; 0/Free Radicals; 10102-43-9/Nitric Oxide; 11061-68-0/Insulin; 17035-90-4/omega-N-Methylarginine; 50-99-7/Glucose; 56-87-1/Lysine; 70-18-8/Glutathione; 74-79-3/Arginine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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