Inhibition of nitric oxide synthase during hemorrhagic shock increases hepatic injury.
The function of nitric oxide (NO) in hemorrhagic shock is controversial. Increased NO synthesis has been temporally correlated with severe shock and has been associated with vascular hyporeactivity to vasoconstrictor agents in isolated vascular rings. Its role in local tissue perfusion, however, is unknown. We studied the role of NO in shock-induced hepatic injury in a rodent model of decompensated hemorrhagic shock by inhibiting its synthesis with Nw-nitro-L-arginine methyl ester (L-NAME). L-NAME infusion (5 micrograms/kg/min) increased the shock-induced hepatic injury and this effect was reversible with L-arginine. L-NAME had only transient effects on systemic mean arterial blood pressure, which quickly returned to pre-L-NAME levels. We conclude that NO synthesis serves a protective function in preventing shock-induced hepatic injury and we postulate that this effect may be due to modulation of the local hepatic circulation.
Harbrecht
B G
BG
Department of Surgery, University of Pittsburgh, Pennsylvania 15213, USA.
Wu
B
B
Watkins
S C
SC
Marshall
H P
HP
Peitzman
A B
AB
Billiar
T R
TR
D000704:Analysis of Variance; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000633:toxicity; D001794:Blood Pressure / Q000187:drug effects; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000633:toxicity*; D007262:Infusions, Intravenous; D008099:Liver / Q000098:blood supply / Q000187:drug effects* / Q000201:enzymology; D008102:Liver Circulation / Q000187:drug effects*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012151:Resuscitation; D012771:Shock, Hemorrhagic / Q000473:pathology / Q000503:physiopathology* / Q000628:therapy; D013997:Time Factors
D004791:Enzyme Inhibitors; D009569:Nitric Oxide; D001120:Arginine; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester