Endotoxin pretreatment enhances portal venous contractile response to endothelin-1

Am J Physiol. 1996 Jan;270(1 Pt 2):H7-15. doi: 10.1152/ajpheart.1996.270.1.H7.


To test whether endotoxin pretreatment modulates the portal hemodynamic response to endothelin (ET)-1 and phenylephrine (PE), two potent vasoconstrictors in the portal circulation of the normal liver, rats received intraperitoneal injections of Escherichia coli lipopolysaccharide (LPS; 1 mg/kg body wt) or saline. Livers were isolated after 6 or 24 h 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) administration. LPS pretreatment increased total portal resistances (Rt), zero-flow pressures (PQ = 0), and linear regression slopes of P-Q relationships, and decreased the sinusoidal diameters (Ds) and sinusoidal volumetric flow (Qv). The response to ET-1 was enhanced 6 and 24 h after LPS administration, leading to greater increases in Rt, PQ = 0, and slope and more pronounced decreases in Dx, red blood cell velocity (VRBC), and Qv. In contrast, PE effects were similar (PQ = 0, slope, Ds) or even attenuated (Rt, VRBC, Qv) in livers from LPS-treated compared with 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Blood Flow Velocity / drug effects
  • Blood Pressure / drug effects
  • Drug Synergism
  • Endothelin-1 / pharmacology*
  • Endotoxins / pharmacology*
  • Erythrocyte Volume / drug effects
  • Erythrocytes / drug effects
  • Erythrocytes / physiology
  • Hemodynamics / drug effects
  • Humans
  • Kinetics
  • Lipopolysaccharides / pharmacology
  • Male
  • Muscle Contraction*
  • Phenylephrine / pharmacology
  • Portal Vein / drug effects*
  • Portal Vein / physiology
  • Rats
  • Rats, Sprague-Dawley
  • Regional Blood Flow / drug effects
  • Vascular Resistance / drug effects


  • Endothelin-1
  • Endotoxins
  • Lipopolysaccharides
  • Phenylephrine