In:
Clinical Science, Portland Press Ltd., Vol. 103, No. s2002 ( 2002-09-01), p. 340S-344S
Abstract:
The receptors underlying the endothelin-dependent component of lung plasma extravasation and leucocyte infiltration induced by oleic acid were assessed in mice. Oleic acid (1mg·kg-1 intravenously), but not endothelin-1 (up to 1nmol·kg-1 intravenously), increased accumulation of Evans blue in the lungs (excluding the trachea and main bronchi) from 11.8±3.9 to 98.6±10.7µg 1h after injection. Bosentan, the antagonist of endothelin receptors (ETA and ETB) or the selective ETB receptor antagonists Ro 46-8443 or A-192621 (administered 1h before oleic acid at doses of 30, 10 and 30mg·kg-1 respectively) reduced the effect of oleic acid by 71%, 58% and 79% respectively. However, the selective ETA receptor antagonist A-127722.5 (10mg·kg-1) was inactive. Oleic acid (2mg·kg-1, intravenously) raised the number of total leucocytes, mononuclear cells and neutrophils in broncho-alveolar lavage fluid 4h after injection. Bosentan and Ro 46-8443 (at doses of 30 and 10mg·kg-1 respectively) inhibited the neutrophil infiltration induced by oleic acid by approx. 80%. None of the antagonists modified control (basal) pulmonary microvascular permeability or total and differential cell counts. Thus, endogenous endothelins, acting via ETB receptor-dependent mechanisms, play a major role in oleic acid-induced lung injury in the mouse by promoting infiltration of circulating neutrophils and enhancement of pulmonary microvascular plasma extravasation. These findings suggest that either ETB or mixed ETA/ETB receptor antagonists might be beneficial in the treatment of the adult respiratory distress syndrome.
Type of Medium:
Online Resource
ISSN:
0143-5221
Language:
English
Publisher:
Portland Press Ltd.
Publication Date:
2002
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