Endothelial Dysfunction in Diabetic Animal Models

The vascular endothelium releases vasodilator substances, endothelium derived relaxing factors (EDRF ; nitric oxide, NO) and endothelium derived hyperpolarizing factor (EDHF), and endothelial dysfunction plays a key role in the pathogenesis of type 1 and type 2 diabetic vascular complications (macrovascular disease and microangiopathy). Impaired endothelium-dependent vasodilation has been demonstrated in various beds of different animal models of diabetes and in humans with type 1 and type 2 . Several mechanisms of endothelial dysfunction have been reported, including substrate ability, impaired release of NO, increased destruction of NO, decreased sensitivity of the vascular smooth muscle to NO, the decreased action of cyclic-AMP and decreased activity of cytochorome P450. The principal mediators of diabetes-associated endothelial dysfunction is increased in oxidized low density lipoprotein (LDL), endothelin-1 (ET-1), oxidative stress, and decreased action of insulin or growth factors in endothelial cells. Correction of these pathways, as well as administration of insulin sensitizer, antioxidants, cholesterol-lowering agents, ET-1 receptor antagonists have been shown to improve endothelium-dependent vasodilation in diabetes. This article synopsises the mechanisms underlying attenuated relaxation response of blood vessels to various agents in diabetic animals.