PMID- 11283857
OWN - NLM
STAT- MEDLINE
DCOM- 20010426
LR  - 20161124
IS  - 0270-9139 (Print)
IS  - 0270-9139 (Linking)
VI  - 33
IP  - 4
DP  - 2001 Apr
TI  - Effect of nitric oxide on shock-induced hepatic heme oxygenase-1 expression in 
      the rat.
PG  - 925-37
AB  - Recent evidence suggests that the hepatic expression of heme oxygenase-1 (HO-1) 
      may preserve hepatocellular integrity after hemorrhagic shock and resuscitation 
      (HR). Because nitric oxide (NO) has been shown to modulate HO-1 expression in 
      cultured cells in vitro, we determined its potential role in the regulation of 
      HO-1 expression after HR in the rat liver in vivo. HO-1 mRNA and protein were 
      highly induced and HO enzyme activity was higher after HR when compared with 
      time-matched sham controls. Administration of the NO donor, molsidomine (MOL) (3 
      mg. kg(-1)), during resuscitation attenuated the accumulation of HO-1 mRNA and 
      protein and the rise in HO activity. In addition, MOL prevented the shock-induced 
      increase in DNA binding activity of the transcription factor, activator protein-1 
      (AP-1), but did not alter the activity of nuclear factor-erythroid 2 related 
      factor (Nrf-2), nuclear transcription factor-kappaB (NF-kappaB), and 
      hypoxia-inducible factor-1 (HIF-1). The suppressing action of MOL was not 
      confined to HO-1, because the hepatic expression of the 70-kd major heat shock 
      protein (HSP) in response to HR was also diminished. Moreover, MOL prevented the 
      HR-induced increase in the serum activity of alanine transaminase (ALT) and 
      alpha-glutathione-S-transferase (alpha-GST) that could otherwise be observed 
      after HR. In contrast, the NO synthase inhibitor, N(omega)-nitro-L-arginine 
      methyl ester (L-NAME) (1 mg.kg(-1)), had either no or only minor effects on the 
      primary experimental endpoints. These findings would be consistent with a 
      reduction of shock-induced liver damage by exogenous NO, which in turn prevents 
      the subsequent activation of injury-sensitive transcription factors, thus 
      attenuating the expression of stress-inducible proteins such as HO-1.
FAU - Hoetzel, A
AU  - Hoetzel A
AD  - Department of Anesthesiology and Critical Care Medicine, University of Freiburg, 
      Germany.
FAU - Vagts, D A
AU  - Vagts DA
FAU - Loop, T
AU  - Loop T
FAU - Humar, M
AU  - Humar M
FAU - Bauer, M
AU  - Bauer M
FAU - Pahl, H L
AU  - Pahl HL
FAU - Geiger, K K
AU  - Geiger KK
FAU - Pannen, B H
AU  - Pannen BH
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Hepatology
JT  - Hepatology (Baltimore, Md.)
JID - 8302946
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (HSP70 Heat-Shock Proteins)
RN  - 0 (Nitric Oxide Donors)
RN  - 0 (Transcription Factors)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - D46583G77X (Molsidomine)
RN  - EC 1.14.14.18 (Heme Oxygenase (Decyclizing))
RN  - EC 1.14.14.18 (Heme Oxygenase-1)
RN  - V55S2QJN2X (NG-Nitroarginine Methyl Ester)
SB  - IM
MH  - Animals
MH  - Blood Pressure/drug effects
MH  - Enzyme Inhibitors/pharmacology
MH  - Gene Expression
MH  - HSP70 Heat-Shock Proteins/metabolism
MH  - Heme Oxygenase (Decyclizing)/genetics/*metabolism
MH  - Heme Oxygenase-1
MH  - Hemodynamics
MH  - Liver/*metabolism/pathology
MH  - Male
MH  - Molsidomine/pharmacology
MH  - NG-Nitroarginine Methyl Ester/pharmacology
MH  - Nitric Oxide/*pharmacology
MH  - Nitric Oxide Donors/pharmacology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Resuscitation
MH  - Shock, Hemorrhagic/*metabolism/pathology/physiopathology
MH  - Transcription Factors/metabolism
EDAT- 2001/04/03 10:00
MHDA- 2001/05/01 10:01
CRDT- 2001/04/03 10:00
PHST- 2001/04/03 10:00 [pubmed]
PHST- 2001/05/01 10:01 [medline]
PHST- 2001/04/03 10:00 [entrez]
AID - S0270-9139(01)04495-0 [pii]
AID - 10.1053/jhep.2001.23431 [doi]
PST - ppublish
SO  - Hepatology. 2001 Apr;33(4):925-37. doi: 10.1053/jhep.2001.23431.