title: Role of endothelin 1 in hemorrhagic shock-induced gastric mucosal injury in rats.
abstract: OBJECTIVE
  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.
authors.affiliation: First Department of Medicine, Osaka University Medical School, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Michida
authors.forename: S
authors.initials: S
authors.lastname: Kawano
authors.forename: E
authors.initials: E
authors.lastname: Masuda
authors.forename: I
authors.initials: I
authors.lastname: Kobayashi
authors.forename: Y
authors.initials: Y
authors.lastname: Nishimura
authors.forename: M
authors.initials: M
authors.lastname: Tsujii
authors.forename: N
authors.initials: N
authors.lastname: Hayashi
authors.forename: Y
authors.initials: Y
authors.lastname: Takei
authors.forename: S
authors.initials: S
authors.lastname: Tsuji
authors.forename: K
authors.initials: K
authors.lastname: Nagano
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D065128:Endothelin Receptor Antagonists; D016232:Endothelins / Q000097:blood / Q000378:metabolism / Q000502:physiology*; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D006439:Hemodynamics / Q000187:drug effects; D007511:Ischemia / Q000473:pathology; D008297:Male; D009994:Osmolar Concentration; D010456:Peptides, Cyclic / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015424:Reperfusion; D012771:Shock, Hemorrhagic / Q000097:blood / Q000473:pathology*; D013270:Stomach / Q000098:blood supply
chemical_list: D065128:Endothelin Receptor Antagonists; D016232:Endothelins; D010456:Peptides, Cyclic; C072247:cyclo(Trp-Asp-Pro-Val-Leu)