Endotoxin pretreatment enhances portal venous contractile response to endothelin-1.
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.
Pannen
B H
BH
Department of Surgery, Johns Hopkins Medical Institutions, Baltimore, Maryland 21287, USA.
Bauer
M
M
Zhang
J X
JX
Robotham
J L
JL
Clemens
M G
MG
D000818:Animals; D001783:Blood Flow Velocity / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D004357:Drug Synergism; D019332:Endothelin-1 / Q000494:pharmacology*; D004731:Endotoxins / Q000494:pharmacology*; D004911:Erythrocyte Volume / Q000187:drug effects; D004912:Erythrocytes / Q000187:drug effects / Q000502:physiology; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D007700:Kinetics; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D009119:Muscle Contraction; D010656:Phenylephrine / Q000494:pharmacology; D011169:Portal Vein / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000187:drug effects; D014655:Vascular Resistance / Q000187:drug effects
D019332:Endothelin-1; D004731:Endotoxins; D008070:Lipopolysaccharides; D010656:Phenylephrine