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 journalArticle

25 Citations (Scopus)

Abstract

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
JournalHypertension
Volume55
Issue number1
DOIs
StatePublished - Jan 1 2010

Fingerprint

Endothelin-1
Blood Vessels
Phenylephrine
Desoxycorticosterone
Aorta
Salts
Acetylglucosaminidase
Acetates
Vasoconstriction
Proteins
Phenylcarbamates
Endothelin-2
Blood Pressure
Hypertension
Carboxylic Acids
Mercury
Peptides

Keywords

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

ASJC Scopus subject areas

  • Internal Medicine

Cite this

Lima, V. V., Giachini, F. R., Carneiro, F. S., Carneiro, Z. N., Saleh, M. A., Pollock, D. M., ... Tostes, R. C. (2010). O-glcnacylation contributes to augmented vascular reactivity induced by endothelin 1. Hypertension, 55(1), 180-188. https://doi.org/10.1161/HYPERTENSIONAHA.109.143818

O-glcnacylation contributes to augmented vascular reactivity induced by endothelin 1. / Lima, Victor V.; Giachini, Fernanda R.; Carneiro, Fernando S.; Carneiro, Zidonia N.; Saleh, Mohamed A.; Pollock, David M.; Fortes, Zuleica B.; Carvalho, Maria Helena C.; Ergul, Adviye; Webb, R Clinton; Tostes, Rita C.

In: Hypertension, Vol. 55, No. 1, 01.01.2010, p. 180-188.

Research output: Contribution to journalArticle

Lima, VV, Giachini, FR, Carneiro, FS, Carneiro, ZN, Saleh, MA, Pollock, DM, Fortes, ZB, Carvalho, MHC, Ergul, A, Webb, RC & Tostes, RC 2010, 'O-glcnacylation contributes to augmented vascular reactivity induced by endothelin 1', Hypertension, vol. 55, no. 1, pp. 180-188. https://doi.org/10.1161/HYPERTENSIONAHA.109.143818
Lima VV, Giachini FR, Carneiro FS, Carneiro ZN, Saleh MA, Pollock DM et al. O-glcnacylation contributes to augmented vascular reactivity induced by endothelin 1. Hypertension. 2010 Jan 1;55(1):180-188. https://doi.org/10.1161/HYPERTENSIONAHA.109.143818
Lima, Victor V. ; Giachini, Fernanda R. ; Carneiro, Fernando S. ; Carneiro, Zidonia N. ; Saleh, Mohamed A. ; Pollock, David M. ; Fortes, Zuleica B. ; Carvalho, Maria Helena C. ; Ergul, Adviye ; Webb, R Clinton ; Tostes, Rita C. / O-glcnacylation contributes to augmented vascular reactivity induced by endothelin 1. In: Hypertension. 2010 ; Vol. 55, No. 1. pp. 180-188.
@article{47f3928c880f4a079fd2a4a3191a4657,
title = "O-glcnacylation contributes to augmented vascular reactivity induced by endothelin 1",
abstract = "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.",
keywords = "Endothelin 1, Hypertension, Vascular reactivity, β-N-acetylglucosamine (O-GlcNAc), β-N-acetylglucosaminidase",
author = "Lima, {Victor V.} and Giachini, {Fernanda R.} and Carneiro, {Fernando S.} and Carneiro, {Zidonia N.} and Saleh, {Mohamed A.} and Pollock, {David M.} and Fortes, {Zuleica B.} and Carvalho, {Maria Helena C.} and Adviye Ergul and Webb, {R Clinton} and Tostes, {Rita C.}",
year = "2010",
month = "1",
day = "1",
doi = "10.1161/HYPERTENSIONAHA.109.143818",
language = "English (US)",
volume = "55",
pages = "180--188",
journal = "Hypertension",
issn = "0194-911X",
publisher = "Lippincott Williams and Wilkins",
number = "1",

}

TY - JOUR

T1 - O-glcnacylation contributes to augmented vascular reactivity induced by endothelin 1

AU - Lima, Victor V.

AU - Giachini, Fernanda R.

AU - Carneiro, Fernando S.

AU - Carneiro, Zidonia N.

AU - Saleh, Mohamed A.

AU - Pollock, David M.

AU - Fortes, Zuleica B.

AU - Carvalho, Maria Helena C.

AU - Ergul, Adviye

AU - Webb, R Clinton

AU - Tostes, Rita C.

PY - 2010/1/1

Y1 - 2010/1/1

N2 - 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.

AB - 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.

KW - Endothelin 1

KW - Hypertension

KW - Vascular reactivity

KW - β-N-acetylglucosamine (O-GlcNAc)

KW - β-N-acetylglucosaminidase

UR - http://www.scopus.com/inward/record.url?scp=73849145046&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=73849145046&partnerID=8YFLogxK

U2 - 10.1161/HYPERTENSIONAHA.109.143818

DO - 10.1161/HYPERTENSIONAHA.109.143818

M3 - Article

C2 - 19948983

AN - SCOPUS:73849145046

VL - 55

SP - 180

EP - 188

JO - Hypertension

JF - Hypertension

SN - 0194-911X

IS - 1

ER -