波生坦可拮抗内皮素-1对大鼠胃血流量及黏膜完整性的影响。

Bosentan antagonizes the effects of endothelin-1 on rat gastric blood flow and mucosal integrity.

作者信息

Lazaratos S, Nakahara A, Goto K, Fukutomi H

机构信息

Department of Internal Medicine, University of Tsukuba, Ibaraki, Japan.

出版信息

Life Sci. 1995;56(9):PL195-200. doi: 10.1016/0024-3205(94)00506-n.

DOI:10.1016/0024-3205(94)00506-n

PMID:7869843

Abstract

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.

摘要

波生坦是一种新型口服有效的混合（ETA+ETB）内皮素受体拮抗剂，最近已被引入并在多种实验模型中进行了测试。我们研究了波生坦对大鼠胃黏膜血流动力学变化和黏膜完整性的影响，这些变化是由外源性应用内皮素-1诱导产生的。对用波生坦（10mg/kg静脉注射）预处理的大鼠注射内皮素-1（500-1000-2000pmol/kg，静脉注射），并监测胃黏膜血流动力学。在用波生坦进行联合口服（30mg/kg）和全身预处理后，我们研究了黏膜下注射内皮素-1（50pmol）对血流量和胃黏膜的影响。波生坦可拮抗内皮素-1在大鼠胃黏膜中的血管舒张、血管收缩和致溃疡作用。这些结果表明，波生坦可能是研究胃肠道内源性内皮素的有用探针。