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Dysfunction in nitric oxide synthesis in streptozotocin treated rat aorta and role of methylglyoxal

Research output: Contribution to journalArticle

  • Yousif A. Shamsaldeen
  • Mahdi H. Alsugoor
  • Lisa A. Lione
  • Christopher D. Benham
Original languageEnglish
Pages (from-to)321-328
Number of pages8
JournalEuropean Journal of Pharmacology
Volume842
Early online date2 Nov 2018
DOIs
DateAccepted/In press - 31 Oct 2018
DateE-pub ahead of print - 2 Nov 2018
DatePublished (current) - 5 Jan 2019

Abstract

Diabetic vascular dysfunction is a major complication of diabetes. Methylglyoxal (MGO) is a dicarbonyl metabolite elevated in diabetic plasma that reacts with interstitial molecules to form advanced glycation end products (AGE). We investigated whether MGO affects the release of nitric oxide (NO) from rat aortic smooth muscle cells (ASMCs), and if L-arginine can prevent these effects of MGO. MGO was significantly elevated in serum from streptozotocin (STZ)-treated rats (121 ± 11.2 µM) compared with vehicle control rats (27.5 ± 9.2 µM). The pathological concentration of MGO (100 μM) was then applied to investigate its effect on inducible nitric oxide synthase (iNOS) expression and NO release on interferon-gamma (IFN-γ) (100 IU/ml) and lipopolysaccharide (LPS) (100 µg/ml)-stimulated control ASMCs. MGO (100 µM) inhibited IFN-γ and LPS-stimulated iNOS expression through inhibiting Akt phosphorylation and inhibition of iNOS expression was prevented by L-arginine (100 µM) co-treatment. These findings show for the first time that MGO inhibits IFN-γ and LPS-stimulated iNOS expression in ASMCs, in addition to inhibiting IFN-γ and LPS-induced Akt phosphorylation. The actions of MGO might contribute to the vascular dysfunction induced by MGO in diabetes.

    Research areas

  • Diabetes mellitus, INOS, L-arginine, Methylglyoxal, Nitric oxide, Vascular dysfunction

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