Short exposure to endotoxin increases the constriction induced by
angiotensin ii in rat aorta.
Christine, Rasetti, and Vicaut Eric.
Laboratoire d'Etude de la Microcirculation, Hop. F. Widal, Paris,
INSERM U141, Hop. F. Widal, Paris
APStracts 2:0360A, 1995.
The contraction elicited by angiotensin II (ANG II) was studied using
standard isometric tension techniques, in aortic rings exposed for 1
hour to 1 or 10 [mu]g/ml E. Coli lipopolysaccharide endotoxin (LPS).
This contraction was 18 and 71% greater for the 2 doses of LPS
respectively than in unexposed control rings. In endothelium-denuded
rings, the LPS-induced increase in contraction in response to ANG II
was completely abolished. Since the contraction induced by ANG II is
modulated by the simultaneous release of prostaglandins, we tested
the hypothesis that LPS interferes with this modulation. We found
that the LPS-induced increase in contraction to ANG II was inhibited
in the presence of the cyclooxygenase inhibitor indomethacin (10-5M),
or of the prostaglandin H2/ thromboxane A2 receptor antagonist
SQ29548 (2x10-7M). Conversely, the LPS-induced increase in
contraction in response to ANG II was not inhibited by the presence
of 10-6M dexamethasone which inhibits new protein synthesis. In
addition, there was no loss of vasodilator response to the
endothelium-dependent receptor agonist acetylcholine (10-8-10-4M), or
in the constrictor responses to norepinephrine (10-9-10-5M) and KCl
(20 to 100 mM). We conclude that short exposure to LPS produces a
specific increase in the constrictor response to ANG II, via
mechanisms mediated by prostaglandin H2/ thromboxane A2. This effect
could be a LPS-induced shift in favor of constrictor prostanoids, in
the balance of dilator/constrictor prostanoids, whose release is
associated with stimulation by ANG II.
Received 17 October 1994; accepted in final form 1 August 1995.
APS Manuscript Number A1067-4.
Article publication pending Journal of Applied Physiology.
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 14 August 1995.