Journal article
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
British journal of pharmacology, Vol.134(1), pp.21-29
09/2001
DOI: 10.1038/sj.bjp.0704216
PMCID: PMC1572916
PMID: 11522593
Abstract
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.
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.
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.
Details
- Title: Subtitle
- 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
- Creators
- Lawrence J Coppey - Veterans Affairs Medical Center, Diabetes Endocrinology Research Center and Department of Internal Medicine, University of Iowa, Iowa City, Iowa, IA 52246, U.S.AJill S Gellett - Veterans Affairs Medical Center, Diabetes Endocrinology Research Center and Department of Internal Medicine, University of Iowa, Iowa City, Iowa, IA 52246, U.S.AEric P Davidson - Veterans Affairs Medical Center, Diabetes Endocrinology Research Center and Department of Internal Medicine, University of Iowa, Iowa City, Iowa, IA 52246, U.S.AJoyce A Dunlap - Veterans Affairs Medical Center, Diabetes Endocrinology Research Center and Department of Internal Medicine, University of Iowa, Iowa City, Iowa, IA 52246, U.S.ADonald D Lund - Veterans Affairs Medical Center, Diabetes Endocrinology Research Center and Department of Internal Medicine, University of Iowa, Iowa City, Iowa, IA 52246, U.S.ADaniela Salvemini - MetaPhore Pharmaceuticals, 1910 Innerbelt Business Center Drive, St. Louis, Missouri, MO 63114, U.S.AMark A Yorek - Veterans Affairs Medical Center, Diabetes Endocrinology Research Center and Department of Internal Medicine, University of Iowa, Iowa City, Iowa, IA 52246, U.S.A
- Resource Type
- Journal article
- Publication Details
- British journal of pharmacology, Vol.134(1), pp.21-29
- DOI
- 10.1038/sj.bjp.0704216
- PMID
- 11522593
- PMCID
- PMC1572916
- ISSN
- 0007-1188
- eISSN
- 1476-5381
- Language
- English
- Date published
- 09/2001
- Academic Unit
- Fraternal Order of Eagles Diabetes Research Center; Endocrinology and Metabolism; Internal Medicine
- Record Identifier
- 9984094723302771
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