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Pharmacological manipulation of vascular endothelium function in non-diabetic and streptozotocin-diabetic rats: effects on nerve conduction, hypoxic resistance and endoneurial capillarization.
Cameron, N E; Cotter, M A; Dines, K C; Maxfield, E K.
Afiliación
  • Cameron NE; Department of Biomedical Sciences, University of Aberdeen, Scotland, UK.
Diabetologia ; 36(6): 516-22, 1993 Jun.
Article en En | MEDLINE | ID: mdl-8335173
We examined the potential for some of the abnormalities of vascular endothelium found in diabetes mellitus to cause neuropathic changes. Non-diabetic rats were treated for 2 months with the cyclo-oxygenase inhibitor flurbiprofen (5 mg.kg-1.day-1) to reduce prostacyclin production, the nitric oxide synthase inhibitor NG-nitro-L-arginine (5 or 25 mg.kg-1.day-1), or combined treatment. There were dose-dependent reductions in sciatic motor and saphenous sensory conduction velocity. The two inhibitors acted synergistically, thus, the 5-6% motor conduction deficits (p < 0.01) produced by either flurbiprofen or NG-nitro-L-arginine (5 mg.kg-1.day-1) increased to 17% (p < 0.001) for combined treatment. With NG-nitro-L-arginine (25 mg.kg-1.day-1) and flurbiprofen, motor and sensory conduction velocity were reduced by 23% (p < 0.001) and 12% (p < 0.001), respectively, matching the deficits following 2-month streptozotocin diabetes. NG-nitro-L-arginine (25 mg.kg-1.day-1) and flurbiprofen together produced a 13% prolongation of the time taken for 80% hypoxic conduction failure in vitro (p < 0.05) and a 10% reduction in sciatic capillary density. A second investigation tested an alternative hypothesis that overproduction of nitric oxide was responsible for vascular-related complications in diabetes, the prediction being that NG-nitro-L-arginine (5 mg.kg-1.day-1) would prevent nerve dysfunction. However, rather than prophylaxis during 2-month streptozotocin diabetes, treatment exacerbated nerve abnormalities.(ABSTRACT TRUNCATED AT 250 WORDS)
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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Nervios Periféricos / Arginina / Nervio Ciático / Capilares / Endotelio Vascular / Flurbiprofeno / Diabetes Mellitus Experimental / Neuropatías Diabéticas / Conducción Nerviosa Límite: Animals Idioma: En Revista: Diabetologia Año: 1993 Tipo del documento: Article Pais de publicación: Alemania
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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Nervios Periféricos / Arginina / Nervio Ciático / Capilares / Endotelio Vascular / Flurbiprofeno / Diabetes Mellitus Experimental / Neuropatías Diabéticas / Conducción Nerviosa Límite: Animals Idioma: En Revista: Diabetologia Año: 1993 Tipo del documento: Article Pais de publicación: Alemania