AR and Hyperglycemia: Many biochemical mechanisms have been proposed to explain the structural and functional abnormalities associated with overexposure of the vascular tissues to hyperglycemia including advanced glycation end products (AGEs), increase in aldose reductase (AR) activity, free radicals acummulation (reactive oxygen intermediate pathway, ROI), resulting in oxidative stress and protein-kinase C activation (PKC) through diacylglycerol accumulation (DAG).