Contraction to endothelin-1 in pulmonary arteries from endotoxin-treated
rats is modulated by the endothelium .
Curzen, Nicholas P, Mark Jd Griffiths, Timothy W Evans.
Unit of Critical Care, National Heart & Lung Institute, London,UK
APStracts 2:0005H, 1995.
Sepsis is characterised by hyporesponsiveness of vascular smooth muscle to
pressor agents. Levels of the potent vasoconstrictor, endothelin-1 (ET-1),
are elevated in animal models of sepsis and in patients. This study assesses
the contractile response of pulmonary artery (PA) from endotoxin-pretreated
rats to ET-1 in order to determine whether this contraction is modified by
the endothelium. Both intact and denuded rings from endotoxin-pretreated rats
exhibited hyporesponsiveness to ET-1, but the endothelium was found to be
essential for maximal ET-1-induced contraction. Upon pretreatment of vessels
with the cyclooxygenase inhibitor indomethacin (10-5M), the novel ETB
receptor antagonist, BQ788 (10-8M and 10-6M) and the thromboxane A2 receptor
antagonist, ICI 192605 (10-5M), each of these agents caused a reduction in
the ET-1-induced contraction of endotoxin-pretreated rat PA only in the
presence of the endothelium, but had no effect in endothelium-denuded vessels
or in sham-treated groups. These findings demonstrate that ET-1-induced
contraction in PA from septic rats is partially dependent upon an
endothelially-derived cyclooxygenase product, the release of which appears to
involve ETB receptor stimulation.
Received 16 August 1994; accepted in final form 5 January 1995.
APS Manuscript Number H0737-4.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 24 February 1995.