The relationship of endothelin-1 and inducible nitric oxide synthase at several stages of the anastomotic healing process

Int Angiol. 2008 Aug;27(4):302-6.

Abstract

Aim: The aim of this study was to investigate the interaction between the endothelin-1 (ET-1) and inducible NO synthase (iNOS) in anastomotic healing.

Methods: The expression of ET-1 and iNOS were investigated by immunohistochemistry in a rat end-to-end arterial anastomotic model. The aorta of 50 male Wistar rats was exposed, then transversely divided and re-anastomosed. The animals were sacrificed immediately after the operation (group A, control group), after 24 h (group B), on 7th postoperative day (group C), on 30th day (group D) and at 6 months (group E). Intima and media thickness and their ratio of the anastomotic segments in each group were calculated from computer digitized images of the individual sections. ET-1 and iNOS expression were measured on a semiquantitative scale ranging from 0 to 3.

Results: ET-1 was expressed from endothelial and smooth muscle cells (SMCs), while iNOs was expressed from SMCs and inflammatory cells. An intense expression of ET-1 was demonstrated mainly at 1 week and to a lesser degree at 1 month. Yet, at 6 months this expression was significantly weakened (P<0.001). In contrast, an intense iNOS expression was identified at 24 h, substantially regressing at statistical significant lower levels after 1 week (P<0.001). Bivariate correlation test showed a positive correlation between ET-1 and iNOS expression.

Conclusion: ET-1 appears to play an important role in intimal thickening during anastomotic healing, especially in the late period of the process. Although there is a positive correlation between ET-1 and iNOS production, the activity of the latter is relatively limited after the first postanastomosis week.

MeSH terms

  • Anastomosis, Surgical
  • Animals
  • Aorta / enzymology
  • Aorta / physiopathology
  • Aorta / surgery*
  • Endothelin-1 / metabolism*
  • Endothelium, Vascular / enzymology
  • Immunohistochemistry
  • Male
  • Models, Animal
  • Muscle, Smooth, Vascular / enzymology
  • Nitric Oxide Synthase Type II / metabolism*
  • Rats
  • Rats, Wistar
  • Time Factors
  • Vascular Surgical Procedures*
  • Wound Healing*

Substances

  • Endothelin-1
  • Nitric Oxide Synthase Type II
  • Nos2 protein, rat