Document Detail


Rapid reversal by aminoguanidine of the neurovascular effects of diabetes in rats: modulation by nitric oxide synthase inhibition.
MedLine Citation:
PMID:  8781303     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Aminoguanidine treatment prevents the development of nerve conduction velocity (NCV) deficits and some renal and retinal complications in diabetic rats. Pharmacological actions include inhibition of the formation of advanced glycosylation end products (AGEs) and nitric oxide (NO) synthase. The aims of the study were to determine the extent to which diabetic NCV and nerve blood flow deficits could be corrected by aminoguanidine in an intervention study, to assess the time course of drug action, and to examine the effects of cotreatment with the NO synthase inhibitor, NG-nitro-L-arginine (NOLA). A 19.3% +/- 0.9% reduction in sciatic motor NCV after 4 weeks of untreated diabetes was corrected 86.6% +/- 3.7% by aminoguanidine treatment for a further 4 weeks. Time-course studies showed that 50% of the maximal effect was attained within 6 days. Sciatic endoneurial capillary blood flow, reduced approximately 45% by diabetes, was corrected 85.6% +/- 12.1% by aminoguanidine treatment. The NCV and blood flow effects of aminoguanidine were completely blocked by cotreatment with NOLA. Thus, the data support a neurovascular mechanism for aminoguanidine involving improved NO action. The rapidity of aminoguanide's effect is consistent with inhibition of free radical production by autoxidative glycosylation or glycoxidation.
Authors:
N E Cameron; M A Cotter
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Metabolism: clinical and experimental     Volume:  45     ISSN:  0026-0495     ISO Abbreviation:  Metab. Clin. Exp.     Publication Date:  1996 Sep 
Date Detail:
Created Date:  1996-10-18     Completed Date:  1996-10-18     Revised Date:  2010-08-25    
Medline Journal Info:
Nlm Unique ID:  0375267     Medline TA:  Metabolism     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1147-52     Citation Subset:  IM    
Affiliation:
Department of Biomedical Sciences, University of Aberdeen, Scotland, UK.
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MeSH Terms
Descriptor/Qualifier:
Animals
Arginine / analogs & derivatives,  therapeutic use
Blood Glucose / analysis
Blood Pressure
Diabetes Mellitus, Experimental / complications*,  physiopathology
Diabetic Angiopathies / complications,  drug therapy*,  physiopathology
Diabetic Neuropathies / complications,  drug therapy*,  physiopathology
Enzyme Inhibitors / therapeutic use*
Glycosylation End Products, Advanced
Guanidines / therapeutic use*
Male
NG-Nitroarginine Methyl Ester
Nitric Oxide Synthase / antagonists & inhibitors
Rats
Rats, Sprague-Dawley
Grant Support
ID/Acronym/Agency:
//Wellcome Trust
Chemical
Reg. No./Substance:
0/Blood Glucose; 0/Enzyme Inhibitors; 0/Glycosylation End Products, Advanced; 0/Guanidines; 50903-99-6/NG-Nitroarginine Methyl Ester; 74-79-3/Arginine; 79-17-4/pimagedine; EC 1.14.13.39/Nitric Oxide Synthase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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