Endothelial cell transfusion ameliorates endothelial dysfunction in 5/6 nephrectomized rats.
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.
['Pacurari|Maricica|M|', 'Xing|Dongqi|D|', 'Hilgers|Rob H P|RH|', 'Guo|Yuan Yuan|YY|', 'Yang|Zhengqin|Z|', 'Hage|Fadi G|FG|']
D000109:Acetylcholine D000581:Amidohydrolases D000818:Animals D001011:Aorta D001120:Arginine D004195:Disease Models, Animal D042783:Endothelial Cells D004730:Endothelium, Vascular D008297:Male D008638:Mesenteric Arteries D009213:Myography D009392:Nephrectomy D052250:Nitric Oxide Synthase Type III D051381:Rats D017207:Rats, Sprague-Dawley D051436:Renal Insufficiency, Chronic D014664:Vasodilation D014665:Vasodilator Agents
endothelial cell chronic kidney disease 5/6 nephrectomy vascular reactivity nitric oxide synthase