Abstract

Pregnant women with diabetes mellitus have a higher incidence of adverse pregnancy outcomes. Vascular, and in particular, endothelial function may be significantly modified in diabetes resulting in impaired endothelium-dependent relaxation. This study aims to investigate endothelium-dependent relaxation in pregnant women with pre-existing type I diabetes mellitus. Small arteries (mean luminal diameter approximately 295 microm) were isolated from biopsies of subcutaneous fat from pregnant women with pre-existing type I diabetes mellitus, non-diabetic pregnant women, and non-diabetic non-pregnant women. Endothelial and smooth muscle function were determined using wire myography, and the contributions of nitric oxide, vasodilator prostanoid and endothelial hyperpolarisation were studied using specific inhibitors. Arteries obtained from the diabetic pregnant women did not demonstrate any difference in either endothelial or smooth muscle function when compared with non-diabetic pregnant women. The contribution of nitric oxide to endothelium-dependent relaxation was approximately 20% in the pregnant women regardless of whether they were diabetic, and approximately 11% in the non-pregnant women. Endothelial hyperpolarisation appeared to contribute largely to vasorelaxation in human subcutaneous arteries, and was at least twice that of nitric oxide in pregnant women and fivefold greater in non-pregnant women. This study provides evidence that pregnant women with well-controlled pre-existing type 1 diabetes mellitus have both normal endothelial and smooth muscle function. Endothelium-dependent hyperpolarisation appears to play a large role in vascular relaxation in human subcutaneous resistance arteries. This study suggests that the problems associated with diabetic pregnancies are unlikely to be due to vascular dysfunction.

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