Endogenous endothelin in a rat model of acute colonic mucosal injury.
BACKGROUND
Endothelin (ET) is involved in various biologic activities in non-vascular and vascular tissues. While ET has some significant effects on gastrointestinal functions, the possible role of endogenous ET in the host response to mucosal injury has not been well clarified.


METHODS
The present study describes an investigation of the effects of an endothelin A receptor antagonist, BQ-123, on lactate dehydrogenase (LDH), mucus and albumin flux into the perfusate in a rat model of acute colonic injury, induced by acetic acid perfusion. The present study also examined localization of ET in damaged rat colons by using immunohistochemistry.


RESULTS
A 4% acetic acid treatment induced mild mucosal damage of perfused rat colon and increased LDH as well as albumin and protein-bound hexose release into the perfusate. Pretreatment with BQ-123 significantly reduced LDH activity and protein-bound hexose concentration in the perfusate and delayed the reduction of albumin leakage from damaged mucosa. Vascular endothelial, neural and surface epithelial cells of the colon showed strong ET-like immunoreactivity. Mucosal damage markedly influenced ET expression by epithelial cells. Mild mucosal damage decreased the ET expression by surface epithelial cells while moderate mucosal damage induced a mosaic location of ET-positive epithelial cells in the crypt. Severe mucosal damage abolished the ET expression by epithelial cells.


CONCLUSIONS
Endothelin may play a role in the host response to acute mucosal damage. Mucosal ET production is significantly affected by mucosal injury.
Sugimachi
M
M
Department of Internal Medicine and Molecular Science, Graduate School of Medicine, Osaka University, Japan.
Kiyohara
T
T
Murayama
Y
Y
Minami
T
T
Miyazaki
Y
Y
Miyagawa
J
J
Shinomura
Y
Y
Matsuzawa
Y
Y
D000085:Acetates / Q000008:administration & dosage; D000818:Animals; D003106:Colon / Q000293:injuries* / Q000378:metabolism / Q000473:pathology; D003627:Data Interpretation, Statistical; D065128:Endothelin Receptor Antagonists; D016232:Endothelins / Q000378:metabolism / Q000502:physiology*; D007124:Immunoenzyme Techniques; D007274:Injections, Intraperitoneal; D007413:Intestinal Mucosa / Q000293:injuries* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D010456:Peptides, Cyclic / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017466:Receptors, Endothelin / Q000008:administration & dosage; D013997:Time Factors
D000085:Acetates; D065128:Endothelin Receptor Antagonists; D016232:Endothelins; D010456:Peptides, Cyclic; D017466:Receptors, Endothelin; C072247:cyclo(Trp-Asp-Pro-Val-Leu)