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Effect of endothelin antagonists, including the novel ET(A) receptor antagonist LBL 031, on endothelin-1 and lipopolysaccharide-induced microvascular leakage in rat airways.

Abstract：

:1. The effect of the novel ET(A) receptor antagonist LBL 031 and other selective and mixed endothelin receptor antagonists on endothelin-1 (ET-1)-induced and lipopolysaccharide (LPS)-induced microvascular leakage was assessed in rat airways. 2. Intravenously administered ET-1 (1 nmole kg(-1)) or LPS (30 mg kg(-1)) caused a significant increase in microvascular leakage in rat airways when compared to vehicle treated animals. 3. Pre-treatment with the selective ET(A) receptor antagonists, LBL 031 or PD 156707, or the mixed ET(A/B) receptor antagonist, bosentan (each at 30 mg kg(-1)), reduced ET-1-induced leakage to baseline levels. ET-1-induced leakage was not reduced by pre-treatment with the ET(B) selective antagonist BQ 788 (3 mg kg(-1)). 4. Pre-treatment with the selective ET(A) receptor antagonist, LBL 031 (0.1 mg kg(-1)) or PD 156707 (10 mg kg(-1)), or the mixed ET(A/B) receptor antagonist, bosentan (30 mg kg(-1)), reduced LPS-induced leakage by 54, 48 and 59% respectively. LPS-induced leakage was not affected by pre-treatment with the ET(B) selective antagonist BQ 788 (3 mg kg(-1)). 5. The data suggests that ET-1-induced microvascular leakage in the rat airway is ET(A) receptor mediated and that part of the increase induced by LPS may be due to the actions of ET-1. Therefore, a potent ET(A) receptor selective antagonist, such as LBL 031, may provide a suitable treatment for inflammatory diseases of the airways, especially those involving LPS and having an exudative phase, such as the septic shock-induced adult respiratory distress syndrome.

journal_name

Br J Pharmacol

journal_title

British journal of pharmacology

authors

Hele DJ,Birrell MA,Webber SE,Foster ML,Belvisi MG

doi

10.1038/sj.bjp.0703691

subject

Has Abstract

pub_date

2000-11-01 00:00:00

pages

1129-34

issue

6

eissn

0007-1188

issn

1476-5381

journal_volume

131

pub_type

杂志文章

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