The importance of vascular epithelial growth factor (VEGF) and inducible nitric oxide synthase (INOS) in rhinitis medicamentosa pathogenesis: An experimental rat model study

Histol Histopathol. 2022 Mar;37(3):261-267. doi: 10.14670/HH-18-399. Epub 2021 Nov 29.

Abstract

Objective: Our aim in this study is to reveal the expression of Vascular Endothelial Growth Factor (VEGF) and Inducible Nitric Oxide Synthase (iNOS) in the pathogenesis of rhinitis medicamentosa (RM), which occurs as a result of the overdose and long-term use of topical nasal decongestants.

Methods: In this study, 24 Wistar albino rats were divided into two groups as experimental and control groups. In the experimental group, 50 µl of 0.05% oxymetazoline (iliadin® merck) was applied intranasally to each nostril three times a day for 2 months with the help of a micropipette. 50 µl saline was applied to the control group. At the end of the second month, the rats were examined. RM was detected in the experimental group. Then the nasal tissues of the rats were removed and fixed with 10% phosphate buffered neutral formaldehyde (pH=7.4). Nasal tissues were decalcified in Morse's solution (10% sodium citrate and 22.5% formic acid). Histopathological evaluations of the preparations were stained using Masson Trichrome (TCM) and Hematoxylin Eosin (H&E) techniques and immunohistochemical examinations of the preparations were stained with VEGF and iNOS antibodies and photographed using the Leica DM6000B microscope and the Leica Application Suite Program.

Results: In the RM group, we found a significant increase in VEGF and iNOS expression in the nasal mucosa compared to the control group (p<0.001). We also observed the main histopathological changes in the nasal mucosa under a light microscope, including squamous metaplasia in the epithelium of the tunica mucosa, submucosal perivascular edema and degeneration of the submucosal glands.

Conclusions: According to these results, increased expression levels of VEGF and iNOS play an important role in rebound swelling in RM pathogenesis.

MeSH terms

  • Animals
  • Edema / pathology
  • Nasal Mucosa / metabolism
  • Nitric Oxide Synthase Type II* / metabolism
  • Oxymetazoline
  • Rats
  • Rats, Wistar
  • Rhinitis* / chemically induced
  • Rhinitis* / pathology
  • Vascular Endothelial Growth Factor A* / metabolism

Substances

  • Vascular Endothelial Growth Factor A
  • vascular endothelial growth factor A, rat
  • Oxymetazoline
  • Nitric Oxide Synthase Type II
  • Nos2 protein, rat