Aminoguanidine, a novel inhibitor of nitric oxide formation, prevents diabetic vascular dysfunction

John A. Corbett, Ronald Tilton, Kathy Chang, Khalid S. Hasan, Yasuo Ido, Jin Lin Wang, Michael A. Sweetland, Jack R. Lancaster, Joseph R. Williamson, Michael L. McDaniel

Research output: Contribution to journalArticle

597 Citations (Scopus)

Abstract

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-1β-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 aminoguanidine 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.

Original languageEnglish (US)
Pages (from-to)552-556
Number of pages5
JournalDiabetes
Volume41
Issue number4
StatePublished - Apr 1992
Externally publishedYes

Fingerprint

Blood Vessels
Nitric Oxide
omega-N-Methylarginine
Glucose
Diabetic Angiopathies
Insulinoma
Diabetes Complications
Nitrites
Interleukin-1
Islets of Langerhans
Arginine
pimagedine
Insulin
Blood Pressure
Cell Line
Proteins

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Corbett, J. A., Tilton, R., Chang, K., Hasan, K. S., Ido, Y., Wang, J. L., ... McDaniel, M. L. (1992). Aminoguanidine, a novel inhibitor of nitric oxide formation, prevents diabetic vascular dysfunction. Diabetes, 41(4), 552-556.

Aminoguanidine, a novel inhibitor of nitric oxide formation, prevents diabetic vascular dysfunction. / Corbett, John A.; Tilton, Ronald; Chang, Kathy; Hasan, Khalid S.; Ido, Yasuo; Wang, Jin Lin; Sweetland, Michael A.; Lancaster, Jack R.; Williamson, Joseph R.; McDaniel, Michael L.

In: Diabetes, Vol. 41, No. 4, 04.1992, p. 552-556.

Research output: Contribution to journalArticle

Corbett, JA, Tilton, R, Chang, K, Hasan, KS, Ido, Y, Wang, JL, Sweetland, MA, Lancaster, JR, Williamson, JR & McDaniel, ML 1992, 'Aminoguanidine, a novel inhibitor of nitric oxide formation, prevents diabetic vascular dysfunction', Diabetes, vol. 41, no. 4, pp. 552-556.
Corbett JA, Tilton R, Chang K, Hasan KS, Ido Y, Wang JL et al. Aminoguanidine, a novel inhibitor of nitric oxide formation, prevents diabetic vascular dysfunction. Diabetes. 1992 Apr;41(4):552-556.
Corbett, John A. ; Tilton, Ronald ; Chang, Kathy ; Hasan, Khalid S. ; Ido, Yasuo ; Wang, Jin Lin ; Sweetland, Michael A. ; Lancaster, Jack R. ; Williamson, Joseph R. ; McDaniel, Michael L. / Aminoguanidine, a novel inhibitor of nitric oxide formation, prevents diabetic vascular dysfunction. In: Diabetes. 1992 ; Vol. 41, No. 4. pp. 552-556.
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AB - 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-1β-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 aminoguanidine 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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