Endothelial dysfunction in diabetes

Endothelial dysfunction plays a key role in the pathogenesis of diabetic va scular disease. The endothelium controls the tone of the underlying vascula r smooth muscle through the production of vasodilator mediators. The endoth elium-derived relaxing factors (EDRF) comprise nitric oxide (NO), prostacyc lin, and a still elusive endothelium-derived hyperpolarizing factor (EDHF). Impaired endothelium-dependent vasodilation has been demonstrated in vario us vascular beds of different animal models of diabetes and in humans with type 1 and 2 diabetes. Several mechanisms of endothelial dysfunction have b een reported, including impaired signal transduction or substrate availibil ity, impaired release of EDRF, increased destruction of EDRF, enhanced rele ase of endothelium-derived constricting factors and decreased sensitivity o f the vascular smooth muscle to EDRF. The principal mediators of hyperglyca emia-induced endothelial dysfunction may be activation of protein kinase C, increased activity of the polyol pathway, non-enzymatic glycation and oxid ative stress. Correction of these pathways, as well as administration of AC E inhibitors and folate, has been shown to improve endothelium-dependent va sodilation in diabetes. Since the mechanisms of endothelial dysfunction app ear to differ according to the diabetic model and the vascular bed under st udy, it is important to select clinically relevant models for future resear ch of endothelial dysfunction.