Journal of Applied Physiology, Vol 79, Issue 6 2094-2100, Copyright © 1995 by American Physiological Society
Short exposure to endotoxin increases the constriction induced by angiotensin II in rat aorta
C. Rasetti and E. Vicaut
Laboratoire d'Etude de la Microcirculation, Hopital Fernand Widal, Paris, France.
The contraction elicited by angiotensin II (ANG II) was studied by using
standard isometric tension techniques in aortic rings exposed for 1 h to 1
or 10 micrograms/ml Escherichia coli lipopolysaccharide endotoxin (LPS).
This contraction was 18 and 71% greater for the two 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. Because 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(-5) M) or the
prostaglandin H2/thromboxane A2-receptor antagonist SQ-29548 (2 x 10(-7)
M). Conversely, the LPS-induced increase in contraction in response to ANG
II was not inhibited by the presence of dexamethasone (10(-6) M), which
inhibits new protein synthesis. In addition, there was no loss of
vasodilator response to the endothelium-dependent receptor agonist
acetylcholine (10(-8)-10(-4) M) or in the constrictor responses to
norepinephrine (10(-9)-10(-5) M) and KCl (20-100 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, the release
of which is associated with stimulation by ANG II.
