Increased vascular O-GlcNAcylation augments reactivity to constrictor stimuli - VASOACTIVE PEPTIDE SYMPOSIUM

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 h with vehicle or PugNAc (O-GlcNAcase inhibitor, 100muM). 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 L-NAME 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 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.