A time-dependent balance between endothelins and nitric oxide
regulating portal resistance after endotoxin.
Pannen, Benedikt H. J., Michael Bauer, Jian X. Zhang, James L.
Robotham, Mark G. Clemens.
Department of Surgery and the Department of Anesthesiology and
Critical Care Medicine, The Johns Hopkins Medical Institutions,
Baltimore, Maryland 21287
APStracts 3:0165H, 1996.
To test whether endothelins are involved in the regulation of portal
resistance after endotoxin pretreatment, and if their effects are
modulated by nitric oxide (NO), rats received i.p. injections of E.
coli lipopolysaccharide (LPS; 1 mg x kg-1 body weight) or saline. Six
and 24 hours later livers were isolated and perfused. Analyses of
portal pressure-flow (P-Q) relationships and epifluorescence
microscopy were performed before and after administration of: A) the
NO synthesis inhibitor N -nitro-L-arginine methyl ester (L-NAME; 10-3
M), followed by L-arginine (2 x 10-3 M); or B) the ETA+B receptor
antagonist bosentan (2 x 10-4 M), followed by L-NAME (10-3 M). LPS
-pretreatment increased all measures of resistance which included
total portal resistance, zero-flow, incremental resistance (slopes of
P-Q relationship), and sinusoid resistance. L-NAME had no effect in
sham controls, but increased all measures of resistance at 6 hours
after LPS, and increased total and incremental resistance 24 hours
after LPS. L-arginine reversed these changes. Bosentan reduced total
and sinusoid resistance slightly in control livers, and caused
substantial reductions in all measures of resistance at 6 and 24
hours after LPS that were partially reversed after L-NAME at 6, but
not at 24 hours. Our data support the hypothesis that a critical
balance between ET-mediated vasoconstrictor influences and NO
-mediated vasodilator influences controls portal resistance after
endotoxin pretreatment.
Received 1 February 1996; accepted in final form 8 April 1996.
APS Manuscript Number H97-6.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 1 May 96