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 β-induced 1) nitrite formation (an oxidation product of NO·) and cGMP accumulation by the rat β-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 ∼ 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.
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April 01 1992
Aminoguanidine, a Novel Inhibitor of Nitric Oxide Formation, Prevents Diabetic Vascular Dysfunction
John A Corbett;
John A Corbett
Department of Pathology, Washington University School of Medicine
St. Louis, Missouri
Department of Chemistry and Biochemistry, Utah State University
Logan, Utah
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Ronald G Tilton;
Ronald G Tilton
Department of Pathology, Washington University School of Medicine
St. Louis, Missouri
Department of Chemistry and Biochemistry, Utah State University
Logan, Utah
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Kathy Chang;
Kathy Chang
Department of Pathology, Washington University School of Medicine
St. Louis, Missouri
Department of Chemistry and Biochemistry, Utah State University
Logan, Utah
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Khalid S Hasan;
Khalid S Hasan
Department of Pathology, Washington University School of Medicine
St. Louis, Missouri
Department of Chemistry and Biochemistry, Utah State University
Logan, Utah
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Yasuo Ido;
Yasuo Ido
Department of Pathology, Washington University School of Medicine
St. Louis, Missouri
Department of Chemistry and Biochemistry, Utah State University
Logan, Utah
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Jin Lin Wang;
Jin Lin Wang
Department of Pathology, Washington University School of Medicine
St. Louis, Missouri
Department of Chemistry and Biochemistry, Utah State University
Logan, Utah
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Michael A Sweetland;
Michael A Sweetland
Department of Pathology, Washington University School of Medicine
St. Louis, Missouri
Department of Chemistry and Biochemistry, Utah State University
Logan, Utah
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Jack R Lancaster, Jr;
Jack R Lancaster, Jr
Department of Pathology, Washington University School of Medicine
St. Louis, Missouri
Department of Chemistry and Biochemistry, Utah State University
Logan, Utah
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Joseph R Williamson;
Joseph R Williamson
Department of Pathology, Washington University School of Medicine
St. Louis, Missouri
Department of Chemistry and Biochemistry, Utah State University
Logan, Utah
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Michael L McDaniel
Michael L McDaniel
Department of Pathology, Washington University School of Medicine
St. Louis, Missouri
Department of Chemistry and Biochemistry, Utah State University
Logan, Utah
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Address correspondence and reprint requests to Michael L. McDaniel, PhD, Department of Pathology, Box 8118, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110.
Diabetes 1992;41(4):552–556
Article history
Received:
December 12 1991
Revision Received:
January 01 1992
Accepted:
January 01 1992
PubMed:
1376704
Citation
John A Corbett, Ronald G Tilton, Kathy Chang, Khalid S Hasan, Yasuo Ido, Jin Lin Wang, Michael A Sweetland, Jack R Lancaster, Joseph R Williamson, Michael L McDaniel; Aminoguanidine, a Novel Inhibitor of Nitric Oxide Formation, Prevents Diabetic Vascular Dysfunction. Diabetes 1 April 1992; 41 (4): 552–556. https://doi.org/10.2337/diab.41.4.552
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