Endotoxin pretreatment enhances the portal venous contractile
response to endothelin-1.
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 2:0267H, 1995.
To test whether endotoxin pretreatment modulates the portal
hemodynamic response to endothelin-1 (ET-1) and phenylephrine (PE),
two potent vasoconstrictors in the portal circulation of the normal
liver, rats received i.p. injections of E. coli lipopolysaccharide
(LPS; 1 mg x kg-1 body weight) or saline. Livers were isolated after
6 or 24 hours and perfused with Krebs buffer containing 5% autologous
erythrocytes. Analyses of portal pressure-flow (P-Q) relationships
and epifluorescence video microscopy were performed before and after
ET-1 (10-9 M) or PE (10-5 M). LPS-pretreatment increased total portal
resistances (Rt), zero-flow pressures (PQ=0), and linear regression
slopes of P-Q relationships, decreased the sinusoidal diameters (DS),
and sinusoidal volumetric flow (QV). Six and 24 hours after LPS the
response to ET-1 was enhanced, leading to greater increases in Rt,
PQ=0, and slope, and more pronounced decreases in DS, VRBC, and QV.
In contrast, PE effects were similar (PQ=0, slope, DS) or even
attenuated (Rt, VRBC, QV) in livers from LPS-treated as compared to
control animals. Thus, endotoxin pretreatment increased the portal
contractile response to ET-1 but not to PE. This enhanced ET-1
response appeared to occur at sinusoidal and presinusoidal levels and
may contribute to endotoxin-induced hepatic microcirculatory failure.
Received 5 April 1995; accepted in final form 12 June 1995.
APS Manuscript Number H326-5.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 11 July 1995.