Ultrastructural changes and immunohistochemical localization of nitric oxide synthase, advanced glycation end products and NF-kappa B in aorta of streptozotocin treated Mongolian gerbils.

Abstract

To evaluate the relationship among the induction of nitric oxide synthase (NOS), advanced glycation end products (AGEs) and NF-kappa B for vascular damage in hyperglycemia, we injected Mongolian gerbils intravenously with 150 mg/kg streptozotocin (STZ) and observed over the next one year the resulting aortic changes by immunohistochemical and electron microscopical techniques. After STZ treatment, hyperglycemia was confirmed and body weight transiently decreased. Morphological observation revealed no remarkable changs in vascular endothelial cells or vascular smooth muscle cells in the aorta at one week after STZ administration. After 4 weeks increased collagen fibrils were observed in the pericellular spaces of media. At one year after STZ administration, increased collagen fibrils and thickened elastic fibers were found around the vascular smooth muscle cells with vacuolization and increased cytoplasmic organellae compared with non-treated animals of the same age. Immunohistochemically endothelial constitutive NOS (ecNOS) was localized in the endothelium of the aorta of Mongolian gerbils. At one year after STZ administration, the reaction products of iNOS, AGEs and NF-kappa B in vascular endothelial cells and smooth muscle cells were much more greatly increased than at one week and 4 weeks. After STZ administration, the localization of NOS, AGEs and NF-kappa B was observed in the aorta, which suggests these factors play important roles in the pathogenesis of vasculopathy in diabetes mellitus.