Role of endothelin 1 in hemorrhagic shock-induced gastric mucosal injury in rats.
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.
Michida
T
T
First Department of Medicine, Osaka University Medical School, Japan.
Kawano
S
S
Masuda
E
E
Kobayashi
I
I
Nishimura
Y
Y
Tsujii
M
M
Hayashi
N
N
Takei
Y
Y
Tsuji
S
S
Nagano
K
K
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
D065128:Endothelin Receptor Antagonists; D016232:Endothelins; D010456:Peptides, Cyclic; C072247:cyclo(Trp-Asp-Pro-Val-Leu)