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 Citations (Scopus)

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
StatePublished - Nov 1 2008

Fingerprint

Blood Vessels
Peptides
Nitric Oxide Synthase Type III
Serotonin Agents
Proteins
Nitroprusside
Phenylephrine
Inbred C57BL Mouse
Acetylcholine
Endothelium
Sprague Dawley Rats
Aorta
Western Blotting

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

Increased vascular O-GlcNAcylation augments reactivity to constrictor stimuli - Vasoactive Peptide Symposium. / Lima, Victor V.; Giachini, Fernanda R.C.; Carneiro, Fernando S.; Carneiro, Zidonia N.; Fortes, Zuleica B.; Carvalho, Maria Helena C.; Webb, R Clinton; Tostes, Rita C.

In: Journal of the American Society of Hypertension, Vol. 2, No. 6, 01.11.2008, p. 410-417.

Research output: Contribution to journalArticle

Lima, Victor V. ; Giachini, Fernanda R.C. ; Carneiro, Fernando S. ; Carneiro, Zidonia N. ; Fortes, Zuleica B. ; Carvalho, Maria Helena C. ; Webb, R Clinton ; Tostes, Rita C. / Increased vascular O-GlcNAcylation augments reactivity to constrictor stimuli - Vasoactive Peptide Symposium. In: Journal of the American Society of Hypertension. 2008 ; Vol. 2, No. 6. pp. 410-417.
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