Soluble epoxide hydrolase inhibitor, t-AUCB, improves salivary gland function by ameliorating endothelial injury

Life Sci. 2022 Nov 1:308:120942. doi: 10.1016/j.lfs.2022.120942. Epub 2022 Sep 9.

Abstract

Aims: Inhibitor of soluble epoxide hydrolase (t-AUCB) has been used in the experimental therapy of hypertension. This study aimed to investigate whether the secretion of submandibular glands (SMGs) altered in renal hypertensive rats, and to explore whether t-AUCB could improve the salivary secretion.

Main methods: 2-kidney 1-clip Sprague-Dawley rats were used as renal hypertensive animals. t-AUCB treatment was given for 1 week after 8 weeks modeling. Blood pressure, blood perfusion and the secretion of SMGs, and endothelium-dependent relaxation of external maxillary artery were measured to investigate the effects of t-AUCB on the vascular tone and the secretion of SMGs in renal hypertensive rats. SMGs were collected for histological evaluation and the internal arteries were dissected for primary endothelial cells culture.

Key findings: The blood perfusion and flow rate of SMGs in the renal hypertensive rats were significantly lower than those in the controls. Endothelium-dependent relaxation of the external maxillary artery and AMPK/Akt/eNOS signaling was impaired in hypertensive rats. The glandular morphology and the concentration of salivary ions did not change obviously. t-AUCB treatment ameliorated the secretion of SMGs, the blood perfusion, and the dysfunction of endothelium-dependent relaxation of the external maxillary artery by activating the AMPK/Akt/eNOS pathway in hypertensive rats.

Significance: t-AUCB increases the blood perfusion through ameliorating dysfunction of endothelium-dependent relaxation of SMGs arteries and thus improves the hyposecretion of SMGs in hypertensive rats.

Keywords: Endothelial injury; Hypertension; Secretion; Submandibular gland.

MeSH terms

  • AMP-Activated Protein Kinases
  • Animals
  • Benzoates
  • Endothelial Cells / metabolism
  • Endothelium / metabolism
  • Enzyme Inhibitors / pharmacology
  • Epoxide Hydrolases* / metabolism
  • Hypertension* / drug therapy
  • Hypertension* / metabolism
  • Proto-Oncogene Proteins c-akt
  • Rats
  • Rats, Sprague-Dawley
  • Salivary Glands / metabolism
  • Urea / analogs & derivatives

Substances

  • 4-(4-(3-adamantan-1-ylureido)cyclohexyloxy)benzoic acid
  • Benzoates
  • Enzyme Inhibitors
  • Urea
  • Proto-Oncogene Proteins c-akt
  • AMP-Activated Protein Kinases
  • Epoxide Hydrolases