Journal of Nippon Medical School: Vol.66 No.3 page.166

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

AuthorList Ryutaro Nishigaki¹⁾, Fang Guo¹⁾, Munehiko Onda¹⁾, Nobutaka Yamada¹⁾, Munehiro Yokoyama¹⁾, Zenya Naito¹⁾, Goro Asano¹⁾, Masumi Shimizu-Suganuma²⁾, Kazuhiro Shichinohe²⁾ and Takumi Aramaki³⁾

Affiliation ¹⁾Department of Pathology, ²⁾Department of Laboratory Animal Science, ³⁾First Department of Internal Medicine, Nippon Medical School

Language EN

Volume 66

Issue 3

Year 1999

Page 166-175

Received November 2, 1998

Accepted February 9, 1999

Keywords nitric oxide synthase (NOS), advanced glycation end products (AGEs), nuclear factor-kappa B (NF-κB), streptozotocin (STZ), Mongolian gerbil

Abstract To evaluate the relationship among the induction of nitric oxide synthase (NOS), advanced glycation end products (AGEs) and NF-κB 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-κB 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-κB was observed in the aorta, which suggests these factors play important roles in the pathogenesis of vasculopathy in diabetes mellitus.

Correspondence to Mailing address; Ryutaro Nishigaki, Department of Pathology, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8602, Japan

ArticleTitle	Ultrastructural changes and immunohistochemical localization of nitric oxide synthase, advanced glycation end products and NF-κB in aorta of streptozotocin treated Mongolian gerbils
AuthorList	Ryutaro Nishigaki¹⁾, Fang Guo¹⁾, Munehiko Onda¹⁾, Nobutaka Yamada¹⁾, Munehiro Yokoyama¹⁾, Zenya Naito¹⁾, Goro Asano¹⁾, Masumi Shimizu-Suganuma²⁾, Kazuhiro Shichinohe²⁾ and Takumi Aramaki³⁾
Affiliation	¹⁾Department of Pathology, ²⁾Department of Laboratory Animal Science, ³⁾First Department of Internal Medicine, Nippon Medical School
Language	EN
Volume	66
Issue	3
Year	1999
Page	166-175
Received	November 2, 1998
Accepted	February 9, 1999
Keywords	nitric oxide synthase (NOS), advanced glycation end products (AGEs), nuclear factor-kappa B (NF-κB), streptozotocin (STZ), Mongolian gerbil
Abstract	To evaluate the relationship among the induction of nitric oxide synthase (NOS), advanced glycation end products (AGEs) and NF-κB 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-κB 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-κB was observed in the aorta, which suggests these factors play important roles in the pathogenesis of vasculopathy in diabetes mellitus.
Correspondence to	Mailing address; Ryutaro Nishigaki, Department of Pathology, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8602, Japan