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O‐GlcNAc‐eNOS is decreased in blood vessels from pregnant Wistar rats, but not in vessels from pregnant SHR
Author(s) -
Troiano Jessica Antonini,
Potje Simone Regina,
Graton Murilo Eduardo,
Silva Daniela Souza,
Antoniali Cristina
Publication year - 2017
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.31.1_supplement.827.17
Subject(s) - enos , phenylephrine , medicine , endocrinology , nitric oxide , mesenteric arteries , endothelium , umbilical vein , chemistry , blood vessel , vasodilation , vasoconstriction , nitric oxide synthase , blood pressure , artery , biochemistry , in vitro
Late pregnancy in spontaneously hypertensive rats (SHR) is related to low blood pressure levels and decreased vasoconstrictors responses to alpha 1‐adrenergic drugs. In blood vessels, increased endothelial nitric oxide synthase (eNOS) phosphorylation and nitric oxide (NO) production are associated to pregnancy effects. Some post‐translational modifications, such as O‐glycosylation by N‐acetyl‐glucosamine (O‐GlcNAc) decreases eNOS activity leading to a lower NO bioavailability. O‐GlcNAc is involved on the OGT (O‐GlcNAc transferase) activity, which binds O‐GlcNAc on serine and threonine residues of target proteins and OGA (O‐GlcNAcase), which removes O‐GlcNAc from these proteins. We hypothesized that O‐GlcNAc‐eNOS is decreased in blood vessels of pregnant SHR. We evaluate the effect of PugNAc, OGA inhibitor, on vascular reactivity to phenylephrine (PE) in aortas of pregnant Wistar rats and in mesenteric artery of pregnant SHR. Methods Aortic rings (2 mm) of non‐pregnant (NP) and pregnant (P) Wistar rats (n= 5–7) and rings of the 2nd and 3rd branches of the mesenteric artery of NP and P SHR (n = 4–6) were incubated in DMEM in the presence of PugNAc (100 μM) or methanol (vehicle) for 24 hours. These rings, with and without endothelium, or with endothelium in the presence of L‐NAME (100 μM, 30 min incubation), were stimulated with increasing and cumulative concentrations of phenylephrine (PE, 1 nM to 10 μM). The results were compared between the groups (ANOVA, p <0.05). Results Pregnancy modulates the vascular reactivity of the blood vessels, reducing the maximum effect of PE curves in aortas from P Wistar rats (22.96 ± 1.36 mN) when compared to the NP Wistar (27.01 ± 0.68), and in mesenteric arteries from P SHR (12.04 ± 0.53 mN) when compared to NP SHR (24.12 ± 0.99 mN). Incubation with PugNAc did not alter the reactivity of NP Wistar aortas to PE (Emax: 26.16 ± 0.43 mN). However, aortas from P Wistar rats incubated with PugNAc showed greater maximum contractile effect to PE (32.75 ± 1.17 mN) when compared to non‐incubated aorta or to NP Wistar aortas. The increased endothelium modulation on PE vasoconstriction observed in aortas from P Wistar rats was reduced by PugNAc when compared to non‐incubated aortas. PugNAc did not alter mesenteric artery rings reactivity to PE in NP SHR (24.66 ± 0.69 mN) or P SHR (13.49 ± 0.71). PugNAc reversed the low reactivity to PE, which is dependent of eNOS activity, in aortas from pregnant Wistar rats, but not in mesenteric arteries from pregnant SHR. Conclusion These results suggest that O‐GlcNAc‐eNOS is decreased in blood vessels from pregnant Wistar rats, but not in vessels from pregnant SHR. Support or Funding Information Financial support: Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) [Grant 2015/08188‐4].