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Endothelial Dysfunction, Macrophage Infiltration and NADPH Oxidase-Dependent Superoxide Production Were Attenuated by Erythropoietin in Streptozotocin-Induced Diabetic Rat Aorta.
MedLine Citation:
PMID:  23154660     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Erythropoietin (EPO) has been used for the management of renal anemia. Recent studies suggest the pleiotropic properties of EPO in various tissues such as brain, kidney and vasculature. Diabetes mellitus is a major risk for development of vascular impairment. The aim of the present study was to investigate the hypothesis that EPO would be beneficial in inhibiting diabetic macroangiopathy. Recombinant human EPO (rHuEPO; 150 U/kg, 3 times/week, s.c.) was administered to streptozotocin-induced diabetic rats for 4 weeks. Streptozotocin (65 mg/kg, i.v.) significantly increased macrophage infiltration and adhesion molecules, monocyte chemoattractant protein-1 and osteopontin mRNA levels in the aorta. These inflammatory changes were suppressed by rHuEPO. Vasodilation in response to acetylcholine in the aortic ring was impaired in the diabetic rats, and improved by rHuEPO. rHuEPO inhibited the aortic expression of mRNA for nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and the NADPH oxidase-dependent superoxide production and the increase in plasma malondialdehyde concentration in diabetic rats. rHuEPO also decreased the level of the receptor for advanced glycation end products in the aorta. We also found an increased expression of phospho-Akt and endothelial nitric oxide synthase and plasma NOx level in the rHuEPO-treated group. On the other hand, rHuEPO did not affect blood glucose levels, hemoglobin A(1c), blood pressure or hematocrit in diabetic rats. These results indicate that rHuEPO exerts pleiotropic antioxidant and anti-inflammatory properties in diabetic rat aorta.
Authors:
Jiahong Wang; Hiroe Toba; Yosuke Morita; Kohei Nakashima; Kazuki Noda; Wei Tian; Miyuki Kobara; Tetsuo Nakata
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-11-15
Journal Detail:
Title:  Pharmacology     Volume:  91     ISSN:  1423-0313     ISO Abbreviation:  Pharmacology     Publication Date:  2012 Nov 
Date Detail:
Created Date:  2012-11-16     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0152016     Medline TA:  Pharmacology     Country:  -    
Other Details:
Languages:  ENG     Pagination:  48-58     Citation Subset:  -    
Copyright Information:
Copyright © 2012 S. Karger AG, Basel.
Affiliation:
Department of Clinical Pharmacology, Division of Pathological Sciences, Kyoto Pharmaceutical University, Kyoto, Japan.
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