title: Endothelial cell transfusion ameliorates endothelial dysfunction in 5/6 nephrectomized rats.
abstract: Endothelial dysfunction is prevalent in chronic kidney disease. This study tested the hypothesis that transfusion of rat aortic endothelial cells (ECs) ameliorates endothelial dysfunction in a rat model of chronic kidney disease. Male Sprague-Dawley rats underwent sham surgery or 5/6 nephrectomy (Nx). Five weeks after Nx, EC (1.5 × 10(6) cells/rat) or vehicle were transfused intravenously. One week later, vascular reactivity of mesenteric artery was assessed on a wire myograph. Sensitivity of endothelium-dependent relaxation to acetylcholine and maximum vasodilation were impaired by Nx and improved by EC transfusion. Using selective pharmacological nitric oxide synthase isoform inhibitors, we demonstrated that the negative effect of Nx on endothelial function and rescue by EC transfusion are, at least in part, endothelial nitric oxide synthase mediated. Plasma asymmetric dimethylarginine was increased by Nx and decreased by EC transfusion, whereas mRNA expression of dimethylarginine dimethylaminohydrolases 1 (DDAH1) was decreased by Nx and restored by EC transfusion. Immunohistochemical staining confirmed that local expression of DDAH1 is decreased by Nx and increased by EC transfusion. In conclusion, EC transfusion attenuates Nx-induced endothelium-dependent vascular dysfunction by regulating DDAH1 expression and enhancing endothelial nitric oxide synthase activity. These results suggest that EC-based therapy could provide a novel therapeutic strategy to improve vascular function in chronic kidney disease.
authors: Vascular Biology and Hypertension Program, Division of Cardiovascular Disease, Department of Medicine, The University of Alabama at Birmingham, Birmingham, Alabama; and.
authors: Maricica
authors: M
authors: Pacurari
authors: Dongqi
authors: D
authors: Xing
authors: Rob H P
authors: RH
authors: Hilgers
authors: Yuan Yuan
authors: YY
authors: Guo
authors: Zhengqin
authors: Z
authors: Yang
authors: Fadi G
authors: FG
authors: Hage
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000581:Amidohydrolases / Q000378:metabolism; D000818:Animals; D001011:Aorta / Q000166:cytology; D001120:Arginine / Q000031:analogs & derivatives; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000637:transplantation*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology*; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects / Q000503:physiopathology*; D009213:Myography; D009392:Nephrectomy; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D051436:Renal Insufficiency, Chronic / Q000503:physiopathology*; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D014665:Vasodilator Agents; C018524:N,N-dimethylarginine; D001120:Arginine; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; D000581:Amidohydrolases; C059999:dimethylargininase; D000109:Acetylcholine
keywords: 5/6 nephrectomy; chronic kidney disease; endothelial cell; nitric oxide synthase; vascular reactivity
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