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Abstract In this work, the role of arginase enzyme in diabetic macrovascular dysfunction (the first stage in diabetic atherosclerosis) was studied. Initiallywe induced two experimental models; diabetic model (by streptozotocin injection) and metabolic syndrome model (by fructose administration). Both of which were accompanied with vascular complications. The effect of arginase inhibition, by L-citrulline, L-norvaline and L-ornithine, during development of vascular complications associated with diabetes and metabolic syndrome was fully investigated;the systolic and diastolic blood pressures were recorded. Vascular reactivity to standard vasoconstrictors; phenylephrine and KCl and vasodilators; acetylcholine and sodium nitroprusside were examined using the isolated artery technique. Serum levels of glucose, insulin, uric acid, triglycerides, total cholesterol and advanced glycation end products were also determined in addition to arginase activity. It was necessary to explain the mechanism of endothelial dysfunction associated with diabetes and the protective effect of arginase inhibition,the basal vascular level of reactive oxygen species as well as the intracellular acetylcholine stimulated nitric oxide generationwere determined. |