Vascular responses to endothelium-dependent vasodilators are greatly i
mpaired in vivo, while isolated blood vessels from animals with diabet
es mellitus demonstrate less consistent degrees of impairment. Glycati
on of proteins, such as hemoglobin, has been implicated in the vascula
r abnormalities associated with diabetes. Objective: The purpose of th
is study was to test the hypothesis that glycosylated hemoglobin is ca
pable of reducing endothelium-dependent vasodilator responses, possibl
y explaining impaired dilation observed in vivo. Methods: To test this
hypothesis, the effect of glycosylated hemoglobin (GH) on vascular re
sponses was studied in several vascular beds, including ventricular mi
crovessels and coronary, mesenteric, femoral, and renal arteries. Coro
nary arterioles were isolated and mounted between two glass pipettes i
n a pressurized (30 cmH(2)O) organ chamber. Isolated artery segments w
ere studied using a standard isometric ring technique. Results: In ven
tricular microvessels, 10 nM nGH (non-GH) and GH both attenuated the r
elaxation to Ach. A lower concentration, 1 nM nGH or GH, did not alter
dilation to Ach. In coronary, femoral, mesenteric and renal artery se
gments, endothelium-dependent responses were not altered by the presen
ce of 10 or 100 nM nGH or GH. Conclusion: In coronary microvessels, an
d coronary, femoral, mesenteric and renal arteries, GH is not responsi
ble for the impaired endothelial function associated with diabetes mel
litus.