Pentoxifylline effects on nerve conduction velocity and blood flow in diabetic rats.
Pentoxifylline has several actions that improve blood rheology and tissue perfusion and may therefore potentially be applicable to diabetic neuropathy. The aims of this study were to ascertain whether 2 weeks of treatment with pentoxifylline could correct nerve conduction velocity and blood flow deficits in 6-week streptozotocin-diabetic rats and to examine whether the effects were blocked by co-treatment with the cyclooxygenase inhibitor, flurbiprofen, or the nitric oxide synthase inhibitor, NG-nitro-L-arginine. Diabetic deficits in sciatic motor and saphenous sensory nerve conduction velocity were 56.5% and 69.8% corrected, respectively, with pentoxifylline treatment. Sciatic endoneurial blood flow was approximately halved by diabetes and this deficit was 50.4% corrected by pentoxifylline. Flurbiprofen co-treatment markedly attenuated these actions of pentoxifylline on nerve conduction and blood flow whereas NG-nitro-L-arginine was without effect. Thus, pentoxifylline treatment confers neurovascular benefits in experimental diabetic neuropathy, which are linked at least in part to cyclooxygenase-mediated metabolism.
Flint
H
H
Department of Biomedical Sciences, Institute of Medical Sciences, University of Aberdeen, Foresterhill, Scotland, UK.
Cotter
M A
MA
Cameron
N E
NE
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D005480:Flurbiprofen / Q000494:pharmacology; D008297:Male; D009431:Neural Conduction / Q000187:drug effects* / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D019335:Nitroarginine / Q000494:pharmacology; D010431:Pentoxifylline / Q000494:pharmacology*; D010525:Peripheral Nerves / Q000098:blood supply* / Q000187:drug effects / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000187:drug effects; D012584:Sciatic Nerve / Q000098:blood supply / Q000187:drug effects / Q000503:physiopathology; D015431:Weight Loss
D001786:Blood Glucose; D016861:Cyclooxygenase Inhibitors; D019335:Nitroarginine; D005480:Flurbiprofen; D019001:Nitric Oxide Synthase; D010431:Pentoxifylline