Nitric oxide as a potential bridge between the metabolic and vascular hypotheses of diabetic neuropathy.
Both metabolic and vascular factors have been invoked in the pathogenesis of diabetic neuropathy but their interrelationships are poorly understood. Both aldose reductase inhibitors and vasodilators improve nerve conduction velocity, nerve blood flow, and (Na+, K+)-ATPase activity in the streptozotocin diabetic rat, implying a metabolic-vascular interaction. Nitric oxide may be the 'bridge' linking these divergent hypotheses of diabetic neuropathy. We propose a model for the pathogenesis of neuropathy invoking metabolic defects both at a vascular and neurochemical level. Early after the induction of experimental diabetes, metabolic defects may lead to a decrease in synthesis of nitric oxide in either the vascular endothelium or the sympathetic ganglia leading to decreased nerve blood flow. In addition, nitric oxide may be involved in more distal defects of somatic nerve metabolism which impair the activity of the nerve Na/K-ATPase by a mechanism involving phosphoinositide signaling and diacyl glycerol and may therefore affect nerve conduction velocity independently of ischaemia. Improved understanding of the effects of hyperglycaemia on nitric oxide metabolism, may provide important clues elucidating the mechanisms underlying the pathogenesis of diabetic neuropathy.
Stevens
M J
MJ
Department of Internal Medicine, University of Michigan, Ann Arbor, USA.
D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology; D003925:Diabetic Angiopathies / Q000503:physiopathology*; D003929:Diabetic Neuropathies / Q000378:metabolism* / Q000503:physiopathology*; D004730:Endothelium, Vascular / Q000502:physiology / Q000503:physiopathology; D005728:Ganglia, Sympathetic / Q000502:physiology / Q000503:physiopathology; D006801:Humans; D008954:Models, Biological; D008955:Models, Cardiovascular; D009420:Nervous System / Q000098:blood supply; D009569:Nitric Oxide / Q000502:physiology*; D051381:Rats
D009569:Nitric Oxide