Title of article :
Effect of α-lipoic acid on vascular responses and nociception in diabetic rats
Author/Authors :
Norman E. Cameron، نويسنده , , Alison M. Jack، نويسنده , , Mary A. Cotter، نويسنده ,
Issue Information :
روزنامه با شماره پیاپی سال 2001
Pages :
11
From page :
125
To page :
135
Abstract :
Oxidative stress contributes to the vascular and neurological complications of diabetes mellitus. The aim was to evaluate the effects of treatment with the radical scavenger and transition metal chelator, α-lipoic acid, on endothelium-dependent relaxation of the mesenteric vasculature and on superior cervical ganglion blood flow in 8 week streptozotocin-induced diabetic rats. α-Lipoic acid effects on small nerve fiber-mediated nociception were also monitored. For the in vitro phenylephrine-precontracted mesenteric vascular bed, diabetes caused a 31% deficit in maximum endothelium-dependent relaxation to acetylcholine, and a 4-fold reduction in sensitivity. α-Lipoic acid gave 85% protection against these defects. Acetylcholine responses are mediated by nitric oxide and endothelium-derived hyperpolarizing factor: isolation of the latter by nitric oxide synthase blockade revealed a 74% diabetic deficit that was halved by α-lipoic acid. Superior cervical ganglion blood flow, 52% reduced by diabetes, was dose-dependently restored by α-lipoic acid (ED50, 44 mg/kg/d). Diabetic rats exhibited mechanical and thermal hyperalgesia, which were abolished by α-lipoic acid treatment. Thus, diabetes impairs nitric oxide and endothelium-derived hyperpolarizing factor-mediated vasodilation. This contributes to reduced neural perfusion, and may be responsible for altered nociceptive function. The effect of α-lipoic acid strongly implicates oxidative stress in these events and suggests a potential therapeutic approach.
Keywords :
EDHF , oxidative stress , Mesenteric vasculature , nitric oxide , Autonomic nervous system , pain , blood flow , free radicals , neuropathy , Vascular endothelium , diabetes mellitus
Journal title :
Free Radical Biology and Medicine
Serial Year :
2001
Journal title :
Free Radical Biology and Medicine
Record number :
518879
Link To Document :
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