Targeting of Rho Kinase Ameliorates Impairment of Diabetic Endothelial Function in Intrarenal Artery

International Journal of Molecular Sciences

Hongping Yin²  Hailong Ru³  Liping Yu⁴  Yanhua Kang³  Guohua Lin³  Chuanfei Liu³  Lixian Sun¹  Liyun Shi³  Qinghua Sun⁵ 

[1]Department of Cardiology, Chengde Medical College, Chengde 067000, China

[2] E-Mail:

[3]Laboratory Center for Medical Science, Hangzhou Normal University, Hangzhou 310036, China

[4] E-Mail:

[5]College of Medicine, Hangzhou Normal University, Hangzhou 310036, China

[6] E-Mails:

[7]Experimental Animal Center, Hangzhou Normal University, Hangzhou 310036, China

[8] E-Mail:

[9]College of Public Health, the Ohio State University, Columbus, OH 43210, USA

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关键词: Rho kinase;    endothelial dysfunction;    diabetic nephropathy;    oxidative stress;   

DOI  :  10.3390/ijms141020282

来源: mdpi

【 摘 要 】

Endothelial dysfunction in kidney vasculature is the initial and key element for nephropathy in diabetes mellitus. Accumulating evidence suggests the protective role of Rho kinase inhibitors in endothelial dysfunction via modulating eNOS activity and NO production. However, the role of Rho kinase in diabetes-related endothelial dysfunction in kidney vasculature and the relevant mechanisms remain unknown. We assessed whether pharmacological inhibition of Rho kinase attenuates endothelial dysfunction in intrarenal arteries from type 1 diabetic rats. Fasudil, a Rho kinase inhibitor effectively decreased the phosphorylated level of MYPT1 without affecting the expression of ROCKs in the kidney. Fasudil treatment showed no improvement in diabetes-related abnormality in metabolic indices, but it significantly ameliorated endothelial dysfunction in intrarenal arteries and lessened the mesangial matrix expansion in the kidney cortex. Mechanistically, superoxide production in the intrarenal artery and NOX4 member of NADPH oxidase in the renal cortex that contribute to diabetic nephropathy were also prevented by the Rho kinase inhibitor. In conclusion, the present results indicate that Rho kinase is involved in endothelial dysfunction in type 1 diabetes via enhancement of oxidative stress and provides new evidence for Rho kinase inhibitors as potential therapeutic agents for the treatment of diabetic nephropathy.

【 授权许可】

CC BY   
© 2013 by the authors; licensee MDPI, Basel, Switzerland