Regulation of hepatic blood flow during resuscitation from hemorrhagic shock: role of NO and endothelins.
We determined the role of nitric oxide (NO) and endothelins (ETs) in the regulation of hepatic blood flow during resuscitation from hemorrhagic shock (HS) in anesthetized rats. Volume resuscitation restored systemic hemodynamics and increased hepatic arterial and portal venous flow above baseline in the vehicle group. Presence of N omega-nitro-L-arginine methyl ester (L-NAME, 1 mg/kg) during resuscitation increased systemic vascular resistance (SVR) above baseline, prevented the restoration of hepatic arterial flow, and abolished portal hyperemia. Although the ETA+B-receptor antagonist bosentan (10 mg/kg) did not alter the systemic hemodynamic response, it abolished the hepatic arterial and portal hyperemia. The ETA-receptor antagonist BQ-610 (150 micrograms/kg) reduced SVR below baseline, allowed hepatic arterial hyperemia to occur, and further enhanced the portal venous hyperemia. This indicates that 1) NO reduces SVR and acts to preserve hepatic blood flow during resuscitation from HS; 2) ETA-receptor-mediated vasoconstriction counteracts the systemic and portal hemodynamic effects of NO; and 3) simultaneous ETB-receptor stimulation enhances blood flow to the liver and may serve to modulate the ETA-receptor-mediated vasoconstrictive effects of ETs.
Pannen
B H
BH
Department of Anesthesiology and Critical Care Medicine, University of Freiburg, Germany.
Bauer
M
M
Nöldge-Schomburg
G F
GF
Zhang
J X
JX
Robotham
J L
JL
Clemens
M G
MG
Geiger
K K
KK
D000818:Animals; D000077300:Bosentan; D016232:Endothelins / Q000097:blood / Q000502:physiology*; D006439:Hemodynamics; D008102:Liver Circulation; D008297:Male; D009566:Nitrates / Q000097:blood; D009569:Nitric Oxide / Q000502:physiology*; D009573:Nitrites / Q000097:blood; D009842:Oligopeptides / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012151:Resuscitation; D012771:Shock, Hemorrhagic / Q000503:physiopathology*; D013449:Sulfonamides / Q000494:pharmacology
D016232:Endothelins; D009566:Nitrates; D009573:Nitrites; D009842:Oligopeptides; D013449:Sulfonamides; C087220:BQ 610; D009569:Nitric Oxide; D000077300:Bosentan