Document Detail


Effect of M40403 treatment of diabetic rats on endoneurial blood flow, motor nerve conduction velocity and vascular function of epineurial arterioles of the sciatic nerve.
MedLine Citation:
PMID:  11522593     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
1. To further explore the effect of antioxidants in preventing diabetes-induced vascular and neural dysfunction we treated streptozotocin-induced diabetic rats daily with subcutaneous injections of 10 mg kg(-1) of M40403 (n=11) and compared the results obtained from 17 control rats and 14 untreated diabetic rats. M40403 is a manganese(II) complex with a bis(cyclo-hexylpyridine)-substituted macrocyclic ligand that was designed to be a selective functional mimetic of superoxide dismutase. Thus, M40403 provides a useful tool to evaluate the roles of superoxide in disease states. 2. Treatment with M40403 significantly improved diabetes-induced decrease in endoneurial blood flow, acetylcholine-mediated vascular relaxation in arterioles that provide circulation to the region of the sciatic nerve, and motor nerve conduction velocity (P<0.05). M40403 treatment also reduced the appearance of superoxide in the aorta and epineurial vessels and peroxynitrite in epineurial vessels. Treating diabetic rats with M40403 reduced the diabetes-induced increase in thiobarbituric acid reactive substances in serum but did not prevent the decrease in lens glutathione level. Treating diabetic rats with M40403 did not improve sciatic nerve Na(+)/K(+) ATPase activity or the sorbitol, fructose or myo-inositol content of the sciatic nerve. 3. These studies provide additional evidence that diabetes-induced oxidative stress and the generation of superoxide and perhaps peroxynitrite may be partially responsible for the development of diabetic vascular and neural complications.
Authors:
L J Coppey; J S Gellett; E P Davidson; J A Dunlap; D D Lund; D Salvemini; M A Yorek
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  British journal of pharmacology     Volume:  134     ISSN:  0007-1188     ISO Abbreviation:  Br. J. Pharmacol.     Publication Date:  2001 Sep 
Date Detail:
Created Date:  2001-08-27     Completed Date:  2001-10-11     Revised Date:  2013-06-09    
Medline Journal Info:
Nlm Unique ID:  7502536     Medline TA:  Br J Pharmacol     Country:  England    
Other Details:
Languages:  eng     Pagination:  21-9     Citation Subset:  IM    
Affiliation:
Veterans Affairs Medical Center, Diabetes Endocrinology Research Center and Department of Internal Medicine, University of Iowa, Iowa City, IA 52246, USA.
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MeSH Terms
Descriptor/Qualifier:
Acetylcholine / pharmacology
Animals
Blood Glucose / drug effects,  metabolism
Blood Vessels / drug effects,  metabolism,  physiopathology
Body Weight / drug effects
Diabetes Mellitus, Experimental / drug therapy*,  metabolism,  physiopathology
Dose-Response Relationship, Drug
Fatty Acids, Nonesterified / blood
Fructose / metabolism
Inositol / metabolism
Male
Manganese
Neural Conduction / drug effects*
Organometallic Compounds / pharmacology*
Rats
Rats, Sprague-Dawley
Regional Blood Flow / drug effects
Sciatic Nerve / blood supply,  drug effects*,  physiopathology
Sodium-Potassium-Exchanging ATPase / drug effects,  metabolism
Sorbitol / metabolism
Superoxides / metabolism
Thiobarbituric Acid Reactive Substances / metabolism
Triglycerides / blood
Tyrosine / analogs & derivatives*,  drug effects,  metabolism
Vasodilation / drug effects
Vasodilator Agents / pharmacology
Grant Support
ID/Acronym/Agency:
DK-25295/DK/NIDDK NIH HHS; DK-58005/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/Blood Glucose; 0/Fatty Acids, Nonesterified; 0/Organometallic Compounds; 0/Thiobarbituric Acid Reactive Substances; 0/Triglycerides; 0/Vasodilator Agents; 11062-77-4/Superoxides; 2Q6R3259KS/imisopasem manganese; 30237-26-4/Fructose; 3604-79-3/3-nitrotyrosine; 50-70-4/Sorbitol; 51-84-3/Acetylcholine; 55520-40-6/Tyrosine; 6917-35-7/Inositol; 7439-96-5/Manganese; EC 3.6.3.9/Sodium-Potassium-Exchanging ATPase
Comments/Corrections

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