Reduction of burn-induced gastric mucosal injury by an endothelin receptor antagonist in rats.
Burn-induced stress ulcers may be a major complication in critically burned patients. The pathophysiology of gastric mucosal ulceration is relatively unknown, however reduced gastric mucosal blood flow is one contributing factor. Endothelin (ET) is a well known vasoconstrictor peptide produced by vascular endothelial cells. Endothelin has been reported to have a fundamental role in the regulation of the systemic circulation. The plasma ET level is increased by burn injury, which also causes thrombosis and vessel occlusion. Endothelin has potent ulcerogenic and vasoconstrictor actions in the stomach where it induces gastric mucosal damage and increases gastric vascular tone. In the present study, we examined the effects of a new non-selective ET receptor antagonist, TAK-044, on burn-induced gastric mucosal injury in rats. Twenty male Sprague-Dawley rats weighting an average of 400 g were burned with hot water (90 degrees C) and then divided into two equal groups. The treatment group received 1 mg/kg of TAK-044 via the dorsal vein of the penis immediately after burn trauma, while the control group received the same volume of saline. Gastric mucosal blood flow was measured with a laser Doppler flowmeter and the area of mucosal necrosis was also determined macroscopically and histologically. Inhibition of ET activity by TAK-044 after burn injury significantly improved microvascular perfusion in the gastric mucosa and prevented the progression of mucosal damage in the stomach (P < 0.05). The present study supports the role of ET in burn-induced gastric ulceration (Curling's ulcer).
Battal
N M
NM
Department of Plastic and Reconstructive Surgery, Kagawa Medical University, Japan.
Hata
Y
Y
Ito
O
O
Matsuda
H
H
Yoshida
Y
Y
Kawazoe
T
T
Nagao
M
M
D000818:Animals; D001783:Blood Flow Velocity; D002056:Burns / Q000150:complications* / Q000503:physiopathology; D004195:Disease Models, Animal; D065128:Endothelin Receptor Antagonists; D005753:Gastric Mucosa / Q000098:blood supply / Q000187:drug effects* / Q000473:pathology; D007262:Infusions, Intravenous; D017078:Laser-Doppler Flowmetry; D008297:Male; D010456:Peptides, Cyclic / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013276:Stomach Ulcer / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology
D065128:Endothelin Receptor Antagonists; D010456:Peptides, Cyclic; C088196:TAK 044