Preventing Superoxide Formation in Epineurial Arterioles of the Sciatic Nerve from Diabetic Rats Restores Endothelium-dependent Vasodilation
Abstract
We have previously reported that in streptozotocin-induced diabetic rats that increased formation of superoxide and peroxynitrite is associated with impairment in vascular relaxation in epineurial arterioles of the sciatic nerve. In this study we demonstrate that pretreating epineurial arterioles from diabetic rats in vitro with alpha-lipoic acid, dihydrolipoic acid, tempol or arginine restores acetylcholine-mediated vascular relaxation to near the reactivity observed in vessels from control rats. Suggesting that increased oxidative stress and reduction in nitric oxide availability is partially responsible for the impairment in endothelium-dependent vasodilation observed in epineurial arterioles from diabetic rats. In contrast, pretreating epineurial arterioles from diabetic rats with aminoguanidine or allopurinol had no effect. Studies designed to investigate the source of superoxide formation provided results suggesting that complex I of the mitochondrial electron transport chain and NAD(P)H oxidase are responsible for the increase in superoxide formation observed with epineurial arterioles from the sciatic nerve. Pretreating epineurial arterioles from diabetic rats with the protein kinase C inhibitor bisindolymaleimide I (GF 109203X) improved acetylcholine-mediated vascular relaxation but did not prevent the increase in superoxide formation suggesting that activation of protein kinase C by oxidative stress is downstream of superoxide formation. These studies imply that increased superoxide formation via the mitochondrial electron transport chain and perhaps NAD(P)H oxidase is partially responsible for reduced vascular reactivity observed in epineurial arterioles of the sciatic nerve from diabetic rats.
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Pretreating epineurial arterioles from diabetic rats with rotenone reduced superoxide formation.
“It was shown that pretreating epineurial arterioles from diabetic rats with rotenone reduced superoxide formation (70).”
From Mitochondrial Dysfunction in Diabetes: From Molecular Mechanisms to Functional Significance and Therapeutic Opportunities (2010) · cites this paper as [70]
Increased superoxide formation via the mitochondrial electron-transport chain and perhaps NAD(P)H oxidase are partially responsible for reduced vascular reactivity observed in epineurial arterioles of the sciatic nerve from diabetic rats.
“These studies imply that increased superoxide formation via the mitochondrial electron-transport chain and perhaps NAD(P)H oxidase are partially responsible for reduced vascular reactivity observed in epineurial arterioles of the sciatic nerve from diabetic rats (70).”
From Mitochondrial Dysfunction in Diabetes: From Molecular Mechanisms to Functional Significance and Therapeutic Opportunities (2010) · cites this paper as [70]
Complex I of the mitochondrial electron-transport chain is responsible for the increase in superoxide formation observed in epineurial arterioles from the sciatic nerve of diabetic rats.
“These studies provided results suggesting that complex I of the mitochondrial electron-transport chain was responsible for the increase in superoxide formation observed with epineurial arterioles from the sciatic nerve of diabetic rats (70).”
From Mitochondrial Dysfunction in Diabetes: From Molecular Mechanisms to Functional Significance and Therapeutic Opportunities (2010) · cites this paper as [70]
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- Authors
- Coppey, L. J., Gellett, J. S., Davidson, E. P., & Yorek, M. A.
- Affiliations
- University of Iowa (US)
- ORCID
- Yorek, Mark A.
- Venue
- Free Radical Research
- Publisher
- Informa UK Limited
- Published
- 2003-01
- Volume
- 37
- Issue
- 1
- Pages
- 33-40
- ISSN
- 1029-2470 (ISSN-L)
- 1071-5762
- OpenAlex
- W1964991169
- Cited by
- 82
- References
- 35
- Citations by year
- 2026: 2 · 2024: 1 · 2023: 3 · 2021: 2 · 2020: 2 · 2019: 1 · 2018: 2 · 2017: 3 · 2016: 3 · 2015: 3 · 2014: 8 · 2013: 4 · 2012: 4
- FWCI
- 2.39
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Free Radical Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Abbott Laboratories
- LifeScan
- National Institute of Diabetes and Digestive and Kidney Diseases (DK-25295, DK-58005, P30DK025295)
- Ethicon
- Topics
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Health Sciences › Medicine › Biochemistry › Antioxidant Activity and Oxidative Stress
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Health and Disease Prevention
- Keywords
- superoxide production, diabetic vascular dysfunction, endothelium-dependent vasodilation, oxidative stress, nitric oxide bioavailability, peroxynitrite, NADPH oxidase, protein kinase C, acetylcholine-induced relaxation, alpha-lipoic acid, tempol, streptozotocin-induced diabetes
- MeSH terms
- Animals, Arginine, Arterioles, Cyclic N-Oxides, Diabetes Mellitus, Experimental, Diabetic Neuropathies, Endothelium, Vascular, Enzyme Inhibitors, Indoles, Thioctic Acid, Male, Maleimides, NADH, NADPH Oxidoreductases, Protein Kinase C, Sciatic Nerve, Spin Labels, Superoxides, Vasodilation, Rats, Sprague-Dawley, Oxidative Stress, NADPH Oxidases, Rats, In Vitro Techniques
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