O-GlcNAcylation contributes to augmented vascular reactivity induced by endothelin 1.

Hypertension
Victor V LimaRita C Tostes

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 mumol/L) produced a time-dependent increase in O-GlcNAc levels and decreased expression of O-GlcNAc transferase and beta-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 mumol/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. Tr...Continue Reading

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Citations

Dec 24, 2010·Cardiovascular Research·Susan A Marsh, John C Chatham
May 10, 2011·American Journal of Physiology. Heart and Circulatory Physiology·Takayuki MatsumotoR Clinton Webb
Jul 11, 2012·American Journal of Physiology. Heart and Circulatory Physiology·Rob H P HilgersSuzanne Oparil
Nov 12, 2010·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Victor V LimaRita C Tostes
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Apr 24, 2013·Hypertension·Joshua S Speed, David M Pollock
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Sep 1, 2011·Journal of Molecular and Cellular Cardiology·Victor M Darley-UsmarJohn C Chatham
Feb 15, 2014·Critical Reviews in Biochemistry and Molecular Biology·Krithika VaidyanathanLance Wells
Sep 14, 2010·Korean Diabetes Journal·Udayakumar Karunakaran, Nam Ho Jeoung
Jan 15, 2017·Cardiovascular Diabetology·Jason Kar Sheng LewRajesh Katare
Dec 1, 2011·Physiological Genomics·Ida G LundeCathrine R Carlson
Jan 20, 2012·Current Opinion in Nephrology and Hypertension·Yohann Rautureau, Ernesto L Schiffrin
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Feb 6, 2020·Biochimica Et Biophysica Acta. Molecular Basis of Disease·Helen E Collins, John C Chatham
Jul 31, 2020·Physiological Reviews·John C ChathamAdam R Wende

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