Cited by 82Nitric Oxide and Endothelin EffectsAntioxidant Activity and Oxidative StressCardiovascular Health and Disease Prevention

Preventing Superoxide Formation in Epineurial Arterioles of the Sciatic Nerve from Diabetic Rats Restores Endothelium-dependent Vasodilation

Coppey, Lawrence J., Gellett, Jill S., Davidson, Eric P., Yorek, Mark A.·2003·Free Radical Research

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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Crossref · 10.1080/1071576021000028442

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Authors
Coppey, L. J., Gellett, J. S., Davidson, E. P., & Yorek, M. A.
Affiliations
University of Iowa (US)
Venue
Free Radical Research
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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