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
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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. British Journal of Pharmacology (2001) 134, 21–29; doi:10.1038/sj.bjp.0704216
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Increased oxidative stress contributes to diabetes-induced vascular and neural disease.
“Further, treating diabetic rats with three different types of antioxidants prevented the diabetes-induced increase in superoxide and peroxynitrite formation in aorta and epineurial arterioles of the sciatic nerve and diabetes-induced vascular and neural dysfunction, thereby providing evidence that increased oxidative stress contributes to diabetes-induced vascular and neural disease (67–69).”
From Mitochondrial Dysfunction in Diabetes: From Molecular Mechanisms to Functional Significance and Therapeutic Opportunities (2010) · cites this paper as [67]
Treating diabetic rats with three different types of antioxidants prevented the diabetes-induced increase in superoxide and peroxynitrite formation in aorta and epineurial arterioles of the sciatic nerve and diabetes-induced vascular and neural dysfunction.
“Further, treating diabetic rats with three different types of antioxidants prevented the diabetes-induced increase in superoxide and peroxynitrite formation in aorta and epineurial arterioles of the sciatic nerve and diabetes-induced vascular and neural dysfunction, thereby providing evidence that increased oxidative stress contributes to diabetes-induced vascular and neural disease (67–69).”
From Mitochondrial Dysfunction in Diabetes: From Molecular Mechanisms to Functional Significance and Therapeutic Opportunities (2010) · cites this paper as [67]
Generation of oxidative stress through superoxide and peroxynitrite impairs vascular function and endothelium-dependent vascular relaxation in epineural arterioles of the sciatic nerve from diabetic rats.
“Studies in our laboratory of epineural arterioles of the sciatic nerve derived from diabetic rats have provided evidence that the generation of oxidative stress through the production of superoxide and peroxynitrite impairs vascular function and endothelium-dependent vascular relaxation (67–69, 342).”
From Mitochondrial Dysfunction in Diabetes: From Molecular Mechanisms to Functional Significance and Therapeutic Opportunities (2010) · cites this paper as [67]
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References 47 · Cited by 91
- Authors
- Coppey, L. J., Gellett, J. S., Davidson, E. P., Dunlap, J. A., Lund, D. D., Salvemini, D., & Yorek, M. A.
- Affiliations
- University of Iowa (US)
- Corresponding author
- Yorek, Mark A
- ORCID
- Yorek, Mark A
- Venue
- British Journal of Pharmacology
- Publisher
- Wiley
- Published
- 2001-09
- Volume
- 134
- Issue
- 1
- Pages
- 21-29
- ISSN
- 0007-1188 (ISSN-L)
- 1476-5381
- PMC
- PMC1572916
- OpenAlex
- W2002607374
- Cited by
- 91
- References
- 47
- Citations by year
- 2024: 2 · 2023: 1 · 2022: 1 · 2021: 1 · 2020: 1 · 2018: 4 · 2017: 4 · 2016: 1 · 2015: 3 · 2014: 4 · 2013: 5
- FWCI
- 3.59
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- British Journal of Pharmacology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- American Diabetes Association
- National Institute of Diabetes and Digestive and Kidney Diseases (DK-25295, R01DK058005, DK-58005, P30DK025295)
- Topics
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Health Sciences › Medicine › Biochemistry › Antioxidant Activity and Oxidative Stress
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Aldose Reductase and Taurine
- Keywords
- manganese(II) complexes, superoxide dismutase mimetic, superoxide, peroxynitrite, oxidative stress, diabetic vascular complications, diabetic neuropathy, motor nerve conduction velocity, sciatic nerve, streptozotocin-induced diabetes, antioxidants
- MeSH terms
- Acetylcholine, Sodium-Potassium-Exchanging ATPase, Animals, Blood Glucose, Blood Vessels, Body Weight, Diabetes Mellitus, Experimental, Dose-Response Relationship, Drug, Fatty Acids, Nonesterified, Fructose, Inositol, Male, Manganese, Neural Conduction, Organometallic Compounds, Regional Blood Flow, Sciatic Nerve, Sorbitol, Superoxides, Triglycerides, Tyrosine, Vasodilation, Vasodilator Agents, Rats, Sprague-Dawley, Thiobarbituric Acid Reactive Substances, Rats
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