Hemorrhagic shock primes the hepatic portal circulation for the vasoconstrictive effects of endothelin-1.
To test whether hemorrhagic shock and resuscitation (HSR) alters the vascular responsiveness of the portohepatic circulation to endothelins (ETs), we studied the macro- and microcirculatory effects of the preferential ET(A) receptor agonist ET-1 and of the selective ET(B) receptor agonist sarafotoxin 6c (S6c) after 1 h of hemorrhagic hypotension and 5 h of volume resuscitation in the isolated perfused rat liver ex vivo using portal pressure-flow relationships and epifluorescence microscopy. Although HSR did not cause major disturbances of hepatic perfusion per se, the response to ET-1 (0.5 x 10(-9) M) was enhanced, leading to greater increases in portal driving pressure, total portal resistance, and zero-flow pressures and more pronounced decreases in portal flow, sinusoidal diameters, and hepatic oxygen delivery compared with time-matched sham shock controls. In sharp contrast, the constrictive response to S6c (0.25 x 10(-9) M) remained unchanged. Thus HSR primes the portohepatic circulation for the vasoconstrictive effects of ET-1 but does not alter the effects of the ET(B) receptor agonist S6c. The enhanced sinusoidal response may contribute to the subsequent development of hepatic microcirculatory failure after secondary insults that are associated with increased generation of ET-1.
Pannen
B H
BH
Department of Anesthesiology and Critical Care Medicine, University of Freiburg, D-79106 Freiburg, Germany. pannen@nz.ukl.uni-freiburg.de
Schroll
S
S
Loop
T
T
Bauer
M
M
Hoetzel
A
A
Geiger
K K
KK
D000818:Animals; D004195:Disease Models, Animal; D019332:Endothelin-1 / Q000494:pharmacology*; D006439:Hemodynamics / Q000187:drug effects; D008099:Liver / Q000098:blood supply / Q000187:drug effects* / Q000503:physiopathology; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D010101:Oxygen Consumption / Q000187:drug effects; D011168:Portal System / Q000187:drug effects* / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin / Q000819:agonists; D012151:Resuscitation; D012771:Shock, Hemorrhagic / Q000503:physiopathology*; D014655:Vascular Resistance / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects*; D014757:Viper Venoms / Q000494:pharmacology
D019332:Endothelin-1; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin; D014757:Viper Venoms; C057354:sarafotoxins s6