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

26 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 Nω-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 AktSer-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
StatePublished - Nov 2008

Keywords

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

ASJC Scopus subject areas

  • Internal Medicine
  • Cardiology and Cardiovascular Medicine

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    Lima, V. V., Giachini, F. R. C., Carneiro, F. S., Carneiro, Z. N., Fortes, Z. B., Carvalho, M. H. C., Webb, R. 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