Pregnancy decreases O-GlcNAc-modified proteins in systemic arteries of normotensive and spontaneously hypertensive rats

Life Sci. 2021 Feb 1:266:118885. doi: 10.1016/j.lfs.2020.118885. Epub 2020 Dec 11.

Abstract

Aim: We determined the role played by O-linked N-acetylglucosamine (O-GlcNAc) of proteins in systemic arteries during late pregnancy in normotensive and hypertensive rats.

Main methods: O-GlcNAc levels and O-GlcNAc modification of endothelial nitric oxide synthase (eNOS) were determined in aorta (conductance vessel) and mesenteric arteries (resistance vessels) of non-pregnant (NP) and pregnant (P) Wistar rats and spontaneously hypertensive rats (SHR). Vascular O-GlcNAc-modified proteins, O-GlcNAcase (OGA) and O-GlcNAc transferase (OGT) expression, and OGA activity were analyzed. Concentration-response to phenylephrine (PE) curves were constructed for arteries with and without endothelium. Arteries were treated with vehicle or PugNAc (OGA inhibitor, 100 μmol/L) in the presence of L-NAME (NOS inhibitor, 100 μmol/L).

Key findings: The content of vascular O-GlcNAc-modified proteins was lower, OGT and OGA expression did not change, and OGA activity was higher in arteries of P-Wistar rats and P-SHR compared to arteries of NP-groups. Reactivity to PE increased in arteries of P-Wistar rats treated with PugNAc compared to vehicle. O-GlcNAcylation of eNOS decreased in P-SHR compared to NP-SHR. PugNAc partially inhibited the effects of endothelium removal and L-NAME on reactivity to PE in arteries of P-Wistar rats. However, PugNAc did not alter reactivity to PE in arteries of P-SHR. Our data showed that pregnancy decreased the content of vascular O-GlcNAc-modified proteins.

Significance: Increased OGA activity and decreased O-GlcNAc modification of eNOS boosts eNOS activity in arteries of P-Wistar rats. In P-SHR, altered OGA activity may lower the content of O-GlcNAc-modified proteins, but decreased OGT activity seems a potential mechanism to reduce glycosylation.

Keywords: Artery; Hypertension; O-GlcNAc; Pregnancy; eNOS.

MeSH terms

  • Acetylglucosamine / chemistry*
  • Animals
  • Aorta, Thoracic / enzymology
  • Aorta, Thoracic / physiopathology*
  • Female
  • Glycosylation
  • Hypertension / enzymology
  • Hypertension / physiopathology*
  • Mesenteric Arteries / enzymology
  • Mesenteric Arteries / physiopathology*
  • N-Acetylglucosaminyltransferases
  • Pregnancy
  • Protein Processing, Post-Translational*
  • Rats
  • Rats, Inbred SHR
  • Rats, Wistar
  • beta-N-Acetylhexosaminidases / chemistry
  • beta-N-Acetylhexosaminidases / metabolism*

Substances

  • N-Acetylglucosaminyltransferases
  • O-GlcNAc transferase
  • hexosaminidase C
  • beta-N-Acetylhexosaminidases
  • Acetylglucosamine