S. Vallejo et al., Highly glycated oxyhaemoglobin impairs nitric oxide relaxations in human mesenteric microvessels, DIABETOLOG, 43(1), 2000, pp. 83-90
Aims/hypothesis. It has been recently shown that glycated human haemoglobin
induces endothelial dysfunction in rat vessels by generating superoxide an
ions that interfere with nitric oxide mediated responses. Our study analyse
d the effect of glycated human haemoglobin on the endothelium-dependent rel
axations of human vessels.
Methods. Omental microvessels were obtained from patients (without diabetes
, hypertension or vascular disease) during surgery and mounted in a small v
essel myograph to study their vasoactive responses (vessels from 3-7 patien
ts for each set of experiments).
Results. Cumulative vasodilatory responses to bradykinin (10 nmol/l to 3 mu
mol/l) were induced in vessels precontracted with 35-50 mmol/l potassium c
hloride. Addition of 100 mu mol/l N-G-nitro-L-arginine methyl ester reduced
the relaxation evoked by bradykinin, but preincubation with both N-G-nitro
-L-arginine methyl ester and 10 mu mol/l indomethacin was needed to abolish
it. Bradykinin-induced responses were inhibited by 1 mu mol/l non-glycated
oxyhaemoglobin whereas no effect was obtained with 10 nmol/l oxyhaemoglobi
n. At these low concentrations (10 nmol/l), glycated human oxyhaemoglobin c
aused an impairment of bradykinin-induced relaxation when the percentage of
glycation was 10% or higher. This effect was prevented by preincubating th
e vessels with ascorbic acid (10 mu mol/l), superoxide dismutase (100 U/ml)
and gliclazide (1 and 10 mu mol/l), but not with indomethacin (10 mu mol/l
), catalase (400-600 U/ml), dimethylthiourea (1 mmol/l) or glibenclamide (1
0 mu mol/l). In vessels preincubated with N-G-nitro-L-arginine methyl ester
(100 mu mol/l), glycohaemoglobin did not add any additional effect.
Conclusion/interpretation. Highly glycated human oxyhaemoglobin, at physiol
ogical plasmatic concentrations, impairs nitric oxide-mediated responses by
a mechanism involving superoxide anions but not cyclooxygenase derivatives
.