title: Effect of alpha-lipoic acid on vascular responses and nociception in diabetic rats.
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, alpha-lipoic acid, on endothelium-dependent relaxation of the mesenteric vasculature and on superior cervical ganglion blood flow in 8 week streptozotocin-induced diabetic rats. alpha-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. alpha-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 alpha-lipoic acid. Superior cervical ganglion blood flow, 52% reduced by diabetes, was dose-dependently restored by alpha-lipoic acid (ED(50), 44 mg/kg/d). Diabetic rats exhibited mechanical and thermal hyperalgesia, which were abolished by alpha-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 alpha-lipoic acid strongly implicates oxidative stress in these events and suggests a potential therapeutic approach.
authors: Department of Biomedical Sciences, University of Aberdeen, Aberdeen, Scotland, UK. n.e.cameron@abdn.ac.uk
authors: N E
authors: NE
authors: Cameron
authors: A M
authors: AM
authors: Jack
authors: M A
authors: MA
authors: Cotter
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001783:Blood Flow Velocity; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D004730:Endothelium, Vascular / Q000187:drug effects; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000502:physiology*; D010146:Pain / Q000503:physiopathology*; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017783:Superior Cervical Ganglion / Q000098:blood supply*; D008063:Thioctic Acid / Q000494:pharmacology*; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000502:physiology*
chemical_list: D000975:Antioxidants; D014662:Vasoconstrictor Agents; D010656:Phenylephrine; D008063:Thioctic Acid