Effects of glycosylated hemoglobin on vascular responses in vitro.

Unlabelled: Vascular responses to endothelium-dependent vasodilators are greatly impaired in vivo, while isolated blood vessels from animals with diabetes mellitus demonstrate less consistent degrees of impairment. Glycation of proteins, such as hemoglobin, has been implicated in the vascular abnormalities associated with diabetes.

Objective: The purpose of this study was to test the hypothesis that glycosylated hemoglobin is capable of reducing endothelium-dependent vasodilator responses, possibly explaining impaired dilation observed in vivo.

Methods: To test this hypothesis, the effect of glycosylated hemoglobin (GH) on vascular responses was studied in several vascular beds, including ventricular microvessels and coronary, mesenteric, femoral, and renal arteries. Coronary arterioles were isolated and mounted between two glass pipettes in a pressurized (30 cmH2O) organ chamber. Isolated artery segments were studied using a standard isometric ring technique.

Results: In ventricular microvessels, 10 nM nGH (non-GH) and GH both attenuated the relaxation to Ach. A lower concentration, 1 nM nGH or GH, did not alter dilation to Ach. In coronary, femoral, mesenteric and renal artery segments, endothelium-dependent responses were not altered by the presence of 10 or 100 nM nGH or GH.

Conclusion: In coronary microvessels, and coronary, femoral, mesenteric and renal arteries, GH is not responsible for the impaired endothelial function associated with diabetes mellitus.