O-glcnacylation contributes to augmented vascular reactivity induced by endothelin 1

Victor V. Lima, Fernanda R. Giachini, Fernando S. Carneiro, Zidonia N. Carneiro, Mohamed A. Saleh, David M. Pollock, Zuleica B. Fortes, Maria Helena C. Carvalho, Adviye Ergul, R. Clinton Webb, Rita C. Tostes

Research output: Contribution to journalArticlepeer-review

32 Scopus citations


O-GlcNAcylation augments vascular contractile responses, and O-GlcNAc-proteins are increased in the vasculature of deoxycorticosterone- acetate salt rats. Because endothelin 1 (ET-1) plays a major role in vascular dysfunction associated with salt-sensitive forms of hypertension, we hypothesized that ET-1-induced changes in vascular contractile responses are mediated by O-GlcNAc modification of proteins. Incubation of rat aortas with ET-1 (0.1 μmol/L) produced a time-dependent increase in O-GlcNAc levels and decreased expression of O-GlcNAc transferase and β-N-acetylglucosaminidase, key enzymes in the O-GlcNAcylation process. Overnight treatment of aortas with ET-1 increased phenylephrine vasoconstriction (maximal effect [in moles]: 19±5 versus 11±2 vehicle). ET-1 effects were not observed when vessels were previously instilled with anti-O-GlcNAc transferase antibody or after incubation with an O-GlcNAc transferase inhibitor (3-[2-adamantanylethyl]- 2-[{4-chlorophenyl}azamethylene]-4-oxo-1,3-thiazaperhyd roine-6-carboxylic acid; 100 μmol/L). Aortas from deoxycorticosterone-acetate salt rats, which exhibit increased prepro-ET-1, displayed increased contractions to phenylephrine and augmented levels of O-GlcNAc proteins. Treatment of deoxycorticosterone- acetate salt rats with an endothelin A antagonist abrogated augmented vascular levels of O-GlcNAc and prevented increased phenylephrine vasoconstriction. Aortas from rats chronically infused with low doses of ET-1 (2 pmol/kg per minute) exhibited increased O-GlcNAc proteins and enhanced phenylephrine responses (maximal effect [in moles]: 18±2 versus 10±3 control). These changes are similar to those induced by O-(2-acetamido-2-deoxy-d- glucopyranosylidene) amino-N-phenylcarbamate, an inhibitor of β-N-acetylglucosaminidase. Systolic blood pressure (in millimeters of mercury) was similar between control and ET-1-infused rats (117±3 versus 123±4 mm Hg; respectively). We conclude that ET-1 indeed augments O-GlcNAc levels and that this modification contributes to the vascular changes induced by this peptide. Increased vascular O-GlcNAcylation by ET-1 may represent a mechanism for hypertension-associated vascular dysfunction or other pathological conditions associated with increased levels of ET-1.

Original languageEnglish (US)
Pages (from-to)180-188
Number of pages9
Issue number1
StatePublished - Jan 2010
Externally publishedYes


  • Endothelin 1
  • Hypertension
  • Vascular reactivity
  • β-N-acetylglucosamine (O-GlcNAc)
  • β-N-acetylglucosaminidase

ASJC Scopus subject areas

  • Internal Medicine


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