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 r eceptor antagonist has been recently introduced and tested in a variet y of experimental models. We studied the effect of bosentan on the cha nges in gastric mucosal hemodynamics and mucosal integrity, induced by the exogenous application of endothelin-1, in rats. Bosentan (10 mg/k g iv) pretreated rats were injected with endothelin-1 (500-1000-2000 p mol/kg, iv) and gastric mucosal hemodynamics were monitored. After com bined oral (30 mg/kg) and systemic pretreatment with bosentan we studi ed the effects of submucosal injection of endothelin-1 (50 pmol) on bl ood flow and gastric mucosa. Bosentan antagonized the vasodilator, vas oconstrictor and ulcerogenic effects of endothelin-1 in the rat gastri c mucosa. These results show that bosentan can be a useful probe in th e study of endogenous endothelin in the gastrointestinal tract.