| Rapid reversal by aminoguanidine of the neurovascular effects of diabetes in rats: modulation by nitric oxide synthase inhibition. | |
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MedLine Citation:
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PMID: 8781303 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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N E Cameron; M A Cotter |
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Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: Metabolism: clinical and experimental Volume: 45 ISSN: 0026-0495 ISO Abbreviation: Metab. Clin. Exp. Publication Date: 1996 Sep |
Date Detail:
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Created Date: 1996-10-18 Completed Date: 1996-10-18 Revised Date: 2010-08-25 |
Medline Journal Info:
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Nlm Unique ID: 0375267 Medline TA: Metabolism Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 1147-52 Citation Subset: IM |
Affiliation:
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Department of Biomedical Sciences, University of Aberdeen, Scotland, UK. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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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:
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//Wellcome Trust |
| Chemical | |
Reg. No./Substance:
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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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