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

Yousif A. Shamsaldeen, Mahdi H. Alsugoor, Lisa A. Lione, Christopher D. Benham

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)321-328
Number of pages8
JournalEuropean Journal of Pharmacology
Publication statusPublished - 2 Nov 2018

Bibliographical note

Funding Information:
The animal care and housing were provided by the animal unit at the University of Hertfordshire, with exceptional care provided by Mrs. Lena Ioannou and Mr. David Clarke. The work was supported by the Ministry of Higher Education of Kuwait and Umm Al-Qura University in Saudi Arabia .


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


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