Bosentan antagonizes the effects of endothelin-1 on rat gastric blood flow and mucosal integrity.
Bosentan, a new type of orally effective, mixed (ETA+ETB) endothelin receptor antagonist has been recently introduced and tested in a variety of experimental models. We studied the effect of bosentan on the changes in gastric mucosal hemodynamics and mucosal integrity, induced by the exogenous application of endothelin-1, in rats. Bosentan (10 mg/kg iv) pretreated rats were injected with endothelin-1 (500-1000-2000 pmol/kg, iv) and gastric mucosal hemodynamics were monitored. After combined oral (30 mg/kg) and systemic pretreatment with bosentan we studied the effects of submucosal injection of endothelin-1 (50 pmol) on blood flow and gastric mucosa. Bosentan antagonized the vasodilator, vasoconstrictor and ulcerogenic effects of endothelin-1 in the rat gastric mucosa. These results show that bosentan can be a useful probe in the study of endogenous endothelin in the gastrointestinal tract.
Lazaratos
S
S
Department of Internal Medicine, University of Tsukuba, Ibaraki, Japan.
Nakahara
A
A
Goto
K
K
Fukutomi
H
H
D000284:Administration, Oral; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D000077300:Bosentan; D065128:Endothelin Receptor Antagonists; D016232:Endothelins / Q000037:antagonists & inhibitors*; D005753:Gastric Mucosa / Q000098:blood supply* / Q000187:drug effects; D007275:Injections, Intravenous; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012039:Regional Blood Flow / Q000187:drug effects; D013276:Stomach Ulcer / Q000139:chemically induced / Q000188:drug therapy; D013449:Sulfonamides / Q000008:administration & dosage / Q000494:pharmacology*
D065128:Endothelin Receptor Antagonists; D016232:Endothelins; D013449:Sulfonamides; D000077300:Bosentan