Increased vascular O-GlcNAcylation augments reactivity to constrictor stimuli - Vasoactive Peptide Symposium

Victor V. Lima, Fernanda R.C. Giachini, Fernando S. Carneiro, Zidonia N. Carneiro, Zuleica B. Fortes, Maria Helena C. Carvalho, R Clinton Webb, Rita C. Tostes

Research output: Contribution to journalArticle

25 Scopus citations

Abstract

O-linked N-acetylglucosaminylation (O-GlcNAcylation) plays a role in many aspects of protein function. Whereas elevated O-GlcNAc levels contribute to diabetes-related end-organ damage, O-GlcNAcylation is also physiologically important. Because proteins that play a role in vascular tone regulation can be O-GlcNAcylated, we hypothesized that O-GlcNAcylation increases vascular reactivity to constrictor stimuli. Aortas from male Sprague-Dawley rats and C57BL/6 mice were incubated for 24 hours with vehicle or PugNAc (O-GlcNAcase inhibitor, 100 μM). PugNAc incubation significantly increased O-GlcNAc proteins, as determined by Western blot. PugNAc also increased vascular contractions to phenylephrine and serotonin, an effect not observed in the presence of N ω -nitro-L-arginine methyl ester or in endothelium-denuded vessels. Acetylcholine-induced relaxation, but not that to sodium nitroprusside, was decreased by PugNAc treatment, an effect accompanied by decreased levels of phosphorylated endothelial nitric oxide synthase (eNOS) Ser-1177 and Akt Ser-473 . Augmented O-GlcNAcylation increases vascular reactivity to constrictor stimuli, possibly due to its effects on eNOS expression and activity, reinforcing the concept that O-GlcNAcylation modulates vascular reactivity and may play a role in pathological conditions associated with abnormal vascular function.

Original languageEnglish (US)
Pages (from-to)410-417
Number of pages8
JournalJournal of the American Society of Hypertension
Volume2
Issue number6
DOIs
Publication statusPublished - Nov 1 2008

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Keywords

  • PugNAc
  • eNOS
  • phosphoinositide-3 kinase
  • potassium chloride

ASJC Scopus subject areas

  • Internal Medicine
  • Cardiology and Cardiovascular Medicine

Cite this

Lima, V. V., Giachini, F. R. C., Carneiro, F. S., Carneiro, Z. N., Fortes, Z. B., Carvalho, M. H. C., ... Tostes, R. C. (2008). Increased vascular O-GlcNAcylation augments reactivity to constrictor stimuli - Vasoactive Peptide Symposium. Journal of the American Society of Hypertension, 2(6), 410-417. https://doi.org/10.1016/j.jash.2008.06.001