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Augmented vascular reactivity induced by ET‐1 is associated with increased O‐GlcNAcylation
Author(s) -
Lima Victor Vitorino,
Giachini Fernanda RC,
Carneiro Fernando S,
Carneiro Zidonia N,
Saleh Mohamed A,
Pollock David M,
Webb R Clinton,
Tostes Rita C
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.627.8
Subject(s) - incubation , phenylephrine , chemistry , vascular smooth muscle , endocrinology , medicine , reactivity (psychology) , biochemistry , pathology , smooth muscle , alternative medicine , blood pressure
O‐GlcNAcylation, the modification of proteins with O‐linked beta‐N‐acetylglucosamine (O‐GlcNAc), modulates many functions including vascular reactivity. We hypothesized that ET‐1‐induced changes in vascular responses are associated with increased levels of O‐GlcNAc‐proteins. Incubation of rat aortas with ET‐1 (0.1 ?M) produced a time‐dependent increase in vascular O‐GlcNAc levels (at 24h, arbitrary units = 2.2±0.1 vs. 1.0±0.05 control; n=4) and decreased expression of OGT and OGA, key enzymes in the O‐GlcNAcylation process. Overnight incubation with ET‐1 increased phenylephrine (PE) reactivity [Emax (mN) = 19±5 vs. 11±2 control; n=4]. The effects of ET‐1 we not observed when vessels were previously transfected with antibodies against‐OGT or after incubation with atrasentan (ETA antagonist, 1μM, Fig.1). Aorta and resistance arteries from rats chronically treated with low doses of ET‐1 (2pmol/min/Kg, for 14 day) exhibit increased O‐GlcNAc‐proteins (Fig.1) and displayed changes in reactivity similar to those induced by PugNAc, an inhibitor of OGA. PugNAc treatment increased O‐GlcNAc levels and enhanced PE responses. Our data show that ET‐1 augments O‐GlcNAc levels and that this modification contributes to the vascular changes induced by this peptide. We speculate that reactive oxygen species may provide a mechanism for the augmented vascular O‐GlcNAc content induced by ET‐1. 1