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.

doi:10.1016/j.jash.2008.06.001

« Previous Next »Journal of the American Society of Hypertension
Volume 2, Issue 6 , Pages 410-417, November 2008

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

Victor V. Lima
- Department of Physiology, Medical College of Georgia, Augusta, Georgia, USA
- Corresponding author: Victor V. Lima, Medical College of Georgia, Department of Physiology, 1120 15^th Street, CA-3141, Augusta, Georgia 30912. Tel: 706-721-0784; fax: 706-721-7299
Fernanda R.C. Giachini, MSc
- Department of Physiology, Medical College of Georgia, Augusta, Georgia, USA
- Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil
Fernando S. Carneiro, MSc
- Department of Physiology, Medical College of Georgia, Augusta, Georgia, USA
- Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil
Zidonia N. Carneiro
- Department of Physiology, Medical College of Georgia, Augusta, Georgia, USA
Zuleica B. Fortes, PhD
- Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil
Maria Helena C. Carvalho, PhD
- Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil
R. Clinton Webb, PhD
- Department of Physiology, Medical College of Georgia, Augusta, Georgia, USA
Rita C. Tostes, PhD
- Department of Physiology, Medical College of Georgia, Augusta, Georgia, USA
- Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil

Received 5 March 2008; accepted 6 June 2008. published online 15 September 2008.

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.

Keywords: PugNAc, eNOS, potassium chloride, phosphoinositide-3 kinase