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Targeting of Rho Kinase Ameliorates Impairment of Diabetic Endothelial Function in Intrarenal Artery
- Source :
- International Journal of Molecular Sciences; Volume 14; Issue 10; Pages: 20282-20298, International Journal of Molecular Sciences, Vol 14, Iss 10, Pp 20282-20298 (2013), International Journal of Molecular Sciences
- Publication Year :
- 2013
- Publisher :
- MDPI AG, 2013.
-
Abstract
- 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.
- Subjects :
- Male
medicine.medical_specialty
Kidney Cortex
Biology
Article
endothelial dysfunction
Catalysis
Diabetes Mellitus, Experimental
Nephropathy
Rats, Sprague-Dawley
lcsh:Chemistry
Inorganic Chemistry
Diabetic nephropathy
Superoxides
Protein Phosphatase 1
Internal medicine
Rho kinase
diabetic nephropathy
oxidative stress
medicine
Animals
Diabetic Nephropathies
Physical and Theoretical Chemistry
Endothelial dysfunction
Protein Kinase Inhibitors
lcsh:QH301-705.5
Molecular Biology
Rho-associated protein kinase
Spectroscopy
rho-Associated Kinases
Kidney
Organic Chemistry
Fasudil
Endothelial Cells
NADPH Oxidases
NOX4
Arteries
General Medicine
medicine.disease
Rats
Computer Science Applications
Diabetes Mellitus, Type 1
Endocrinology
medicine.anatomical_structure
lcsh:Biology (General)
lcsh:QD1-999
NADPH Oxidase 4
Rho kinase inhibitor
Subjects
Details
- ISSN :
- 14220067
- Volume :
- 14
- Database :
- OpenAIRE
- Journal :
- International Journal of Molecular Sciences
- Accession number :
- edsair.doi.dedup.....ab31054a8fbf119d64c0910c0d20900b