Document Detail


Aminoguanidine, a novel inhibitor of nitric oxide formation, prevents diabetic vascular dysfunction.
MedLine Citation:
PMID:  1376704     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Increased blood flow and vascular leakage of proteins preferentially affect tissues that are sites of diabetic complications in humans and animals. These vascular changes in diabetic rats are largely prevented by aminoguanidine. Glucose-induced vascular changes in nondiabetic rats are also prevented by aminoguanidine and by NG-monomethyl-L-arginine (NMMA), an established inhibitor of nitric oxide (NO.) formation from L-arginine. Aminoguanidine and NMMA are equipotent inhibitors of interleukin-1 beta-induced 1) nitrite formation (an oxidation product of NO.) and cGMP accumulation by the rat beta-cell insulinoma cell line RINm5F, and 2) inhibition of glucose-stimulated insulin secretion and formation of iron-nitrosyl complexes by islets of Langerhans. In contrast, NMMA is approximately 40 times more potent than aminoquanidine in elevating blood pressure in nondiabetic rats. These results demonstrate that aminoguanidine inhibits NO. production and suggest a role for NO. in the pathogenesis of diabetic vascular complications.
Authors:
J A Corbett; R G Tilton; K Chang; K S Hasan; Y Ido; J L Wang; M A Sweetland; J R Lancaster; J R Williamson; M L McDaniel
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Diabetes     Volume:  41     ISSN:  0012-1797     ISO Abbreviation:  Diabetes     Publication Date:  1992 Apr 
Date Detail:
Created Date:  1992-07-23     Completed Date:  1992-07-23     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0372763     Medline TA:  Diabetes     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  552-6     Citation Subset:  AIM; IM    
Affiliation:
Department of Pathology, Washington University School of Medicine, St Louis, Missouri 63110.
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MeSH Terms
Descriptor/Qualifier:
Amino Acid Oxidoreductases / antagonists & inhibitors,  metabolism
Animals
Arginine / analogs & derivatives,  pharmacology
Blood Pressure / drug effects
Blood Vessels / drug effects
Cells, Cultured
Diabetic Angiopathies / etiology,  metabolism,  prevention & control*
Enzyme Activation / drug effects,  physiology
Glucose / pharmacology
Guanidines / pharmacology*
Insulin / metabolism
Interleukin-1 / pharmacology
Islets of Langerhans / cytology,  drug effects,  metabolism
Male
Nitric Oxide / antagonists & inhibitors,  metabolism*
Nitric Oxide Synthase
Rats
Rats, Inbred Strains
Regional Blood Flow / drug effects
omega-N-Methylarginine
Grant Support
ID/Acronym/Agency:
DK-06181/DK/NIDDK NIH HHS; EY-06600/EY/NEI NIH HHS; T32 DK-07296/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/Guanidines; 0/Interleukin-1; 10102-43-9/Nitric Oxide; 11061-68-0/Insulin; 17035-90-4/omega-N-Methylarginine; 50-99-7/Glucose; 74-79-3/Arginine; 79-17-4/pimagedine; EC 1.14.13.39/Nitric Oxide Synthase; EC 1.4.-/Amino Acid Oxidoreductases

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


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