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Highly glycated oxyhaemoglobin impairs nitric oxide relaxations in human mesenteric microvessels.

Abstract：

AIMS/HYPOTHESIS:It has been recently shown that glycated human haemoglobin induces endothelial dysfunction in rat vessels by generating superoxide anions that interfere with nitric oxide mediated responses. Our study analysed the effect of glycated human haemoglobin on the endothelium-dependent relaxations of human vessels. METHODS:Omental microvessels were obtained from patients (without diabetes, hypertension or vascular disease) during surgery and mounted in a small vessel myograph to study their vasoactive responses (vessels from 3-7 patients for each set of experiments). RESULTS:Cumulative vasodilatory responses to bradykinin (10 nmol/l to 3 mumol/l) were induced in vessels precontracted with 35-50 mmol/l potassium chloride. Addition of 100 mumol/l NG-nitro-L-arginine methyl ester reduced the relaxation evoked by bradykinin, but preincubation with both NG-nitro-L-arginine methyl ester and 10 mumol/l indomethacin was needed to abolish it. Bradykinin-induced responses were inhibited by 1 mumol/l non-glycated oxyhaemoglobin whereas no effect was obtained with 10 nmol/l oxyhaemoglobin. At these low concentrations (10 nmol/l), glycated human oxyhaemoglobin caused an impairment of bradykinin-induced relaxation when the percentage of glycation was 10% or higher. This effect was prevented by preincubating the vessels with ascorbic acid (10 mumol/l), superoxide dismutase (100 U/ml) and gliclazide (1 and 10 mumol/l), but not with indomethacin (10 mumol/l), catalase (400-600 U/ml), dimethylthiourea (1 mmol/l) or glibenclamide (10 mumol/l). In vessels preincubated with NG-nitro-L-arginine methyl ester (100 mumol/l), glycohaemoglobin did not add any additional effect. CONCLUSION/INTERPRETATION:Highly glycated human oxyhaemoglobin, at physiological plasmatic concentrations, impairs nitric oxide-mediated responses by a mechanism involving superoxide anions but not cyclooxygenase derivatives.

journal_name

Diabetologia

journal_title

Diabetologia

authors

Vallejo S,Angulo J,Peiró C,Nevado J,Sánchez-Ferrer A,Petidier R,Sánchez-Ferrer CF,Rodríguez-Mañas L

doi

10.1007/s001250050011

subject

Has Abstract

pub_date

2000-01-01 00:00:00

pages

83-90

issue

eissn

0012-186X

issn

1432-0428

pii

00430083.125

journal_volume

pub_type

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Highly glycated oxyhaemoglobin impairs nitric oxide relaxations in human mesenteric microvessels.