Diabetic vascular disease is accompanied by decreased formation of the vasodilators nitric oxide and prostacyclin and increased formation of vasoconstrictor eicosanoids. The alteration in function is caused by exposure of endothelial cells to elevated glucose and its effect to increase the formation of oxygenderived free radicals. These in turn cause nitric oxide synthase to produce peroxynitrite, a damaging molecule. This inactivates prostacyclin synthase, leading to the accumulation of eicosanoids. These endothelium-derived constrictor factors (EDCF) also increase endothelial cell adhesion molecules and atherosclerotic lesions. The abnormalities can be prevented by adequate scavenging of oxygenderived free radicals or by blocking the actions of the eicosanoids at thromboxane-prostanoid (TP) receptors...