Role of endothelin 1 in hemorrhagic shock-induced gastric mucosal injury in rats

Gastroenterology. 1994 Apr;106(4):988-93. doi: 10.1016/0016-5085(94)90758-7.

Abstract

Background/aims: Gastric microcirculatory disturbances are involved in the pathogenesis of stress ulcers; however, vasomodulators regulating this process are not fully understood. This study was conducted to investigate the role of endothelin 1 (ET-1) in hemorrhagic shock-induced gastric mucosal damage in rats.

Methods: ET-1 contents in plasma and gastric mucosa were measured and gastric mucosal damage was evaluated during a control period, 60 minutes of ischemia, 15 minutes of reperfusion, and 30 minutes of postreperfusion. Next, effects of BQ-123, an endothelinA receptor antagonist, on the gastric mucosal damage and hemodynamics were studied.

Results: Both plasma and mucosal ET-1 significantly increased after ischemia and reperfusion compared with the control values, but only mucosal ET-1 continued to increase after reperfusion, leading to the development of gastric mucosal damage. BQ-123, administered just before reperfusion, reduced mucosal damage in the postreperfusion period dose-dependently and improved mean gastric mucosal blood flow and mucosal hemoglobin oxygen saturation during the 30-minute postreperfusion period.

Conclusions: These results suggest that endogenous ET-1 plays an important role in the pathogenesis of hemorrhage shock-induced gastric mucosal damage through impairment of mucosal microcirculation. Further, endothelinA antagonists may have therapeutic benefits for shock-induced gastric mucosal damage.

MeSH terms

  • Animals
  • Dose-Response Relationship, Drug
  • Endothelin Receptor Antagonists
  • Endothelins / blood
  • Endothelins / metabolism
  • Endothelins / physiology*
  • Gastric Mucosa / drug effects
  • Gastric Mucosa / metabolism
  • Gastric Mucosa / pathology*
  • Hemodynamics / drug effects
  • Ischemia / pathology
  • Male
  • Osmolar Concentration
  • Peptides, Cyclic / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Reperfusion
  • Shock, Hemorrhagic / blood
  • Shock, Hemorrhagic / pathology*
  • Stomach / blood supply

Substances

  • Endothelin Receptor Antagonists
  • Endothelins
  • Peptides, Cyclic
  • cyclo(Trp-Asp-Pro-Val-Leu)