The NO donor sodium nitroprusside reverses the negative effects on hepatic arterial flow induced by endotoxin and the NO synthase inhibitor L-NAME.
In previous studies we have observed that the nitric oxide synthase inhibitor L-NAME induces a profound deterioration of liver circulation in experimental endotoxemia. Using the same porcine model we now have evaluated the possibility of modulating these effects with the nitric oxide donor sodium nitroprusside. Infusion of endotoxin led to a gradual deterioration of hemodynamic parameters, including liver blood flow. The decreases in portal blood flow paralleled and matched the decreases in cardiac output, and no compensatory increase in hepatic arterial flow occurred. L-NAME had detrimental effects on hemodynamics, including the liver circulation. The latter effects could, however, partially be reversed by sodium nitroprusside. Hepatic arterial flow increased from 1.9 to 7.2 ml/kg/min, with a concomitant decrease in hepatic arterial resistance from 5,364 to 1,746 dyn s/cm5 kg. A control group exhibited no significant change in either flow or resistance. The response to sodium nitroprusside was rapid and vigorous, and probably largely due to relaxation of the hepatic arterioles, and not to abatement of intrahepatic edema or plugging of the sinusoids. Furthermore, we conclude that the endotoxin-induced dysfunction of the hepatic arterial buffer response may be due to a selective inhibition of vascular endothelial function.
Gundersen
Y
Y
Institute for Surgical Research, Rikshospitalet, National Hospital, Oslo, Norway.
Saetre
T
T
Scholz
T
T
Carlsen
H
H
Kjekshus
H
H
Smiseth
O A
OA
Lilleaasen
P
P
Aasen
A O
AO
D000818:Animals; D001158:Arteries / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D004731:Endotoxins / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D006400:Hematocrit; D006439:Hemodynamics / Q000187:drug effects; D008102:Liver Circulation / Q000187:drug effects*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D009599:Nitroprusside / Q000494:pharmacology*; D013552:Swine; D014655:Vascular Resistance / Q000187:drug effects
D004731:Endotoxins; D004791:Enzyme Inhibitors; D009599:Nitroprusside; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester