Effects of tumor necrosis factor and interleukin 1 on the
constriction induced by angiotensin ii in rat aorta.
Vicaut, Eric, Christine Rasetti, and Nathalie Baudry.
Laboratoire d'Etude de la Microcirculation, Hop. F. Widal, 200 rue
du Fg-St Denis 75010 Paris, France, INSERM U141, Hop. F. Widal,
Paris
APStracts 3:0032H, 1996.
In order to better understand, the different steps in the changes
occurring in vascular reactivity during sepsis,we studied the effects
of a short exposure to tumor necrosis factor (TNF) and Interleukin 1
(IL-1) on the contraction in response to angiotensin II (ANG II). The
contraction elicited by angiotensin II (ANG II) was studied using
standard isometric tension techniques, in aortic rings exposed for 1
hour to 25 ng/ml (TNF), or to 5 or 20 ng/ml (IL-1). This contraction
was not significantly changed by TNF, but was 109 +/- 23 % and 190+/-
38% greater than in control rings after 5 and 20 ng/ml respectively
of IL-1. Since the contraction induced by ANG II is modulated by the
simultaneous release of prostaglandins, we tested the hypothesis that
IL-1 interferes with this modulation. We found that the IL-1-induced
increase in contraction in response to ANG II was completely
inhibited by 10-5M of the cyclooxygenase inhibitor indomethacin and
also by 10-5M of the prostaglandin H2/ thromboxane A2 receptor
antagonist SQ29548. Note however, that in rings exposed to IL-1 the
contraction in response to the thromboxane A2 receptor agonist U46619
was not significantly different from the contraction in unexposed
rings. Furthermore, no loss was observed in either the vasodilator
response to 10-9 to 10-4M of the endothelium-dependent receptor
agonist acetylcholine, or in the receptor independent contraction
induced by 60 mM K+. We conclude that short exposure to IL-1, but not
to TNF, produces a specific increase in the vasoconstrictor response
to ANG II via mechanisms mediated by prostaglandin H2/ thromboxane
A2. This increase might result from an interleukin-1-induced shift in
favor of constrictor prostanoids, in the balance of the
dilator/constrictor prostanoids whose release is associated with
stimulation by ANG II.
Received 6 September 1995; accepted in final form 4 January 1996.
APS Manuscript Number H972-5.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 25 January 96