PMID- 11776329
OWN - NLM
STAT- MEDLINE
DCOM- 20020712
LR  - 20201208
IS  - 0340-6245 (Print)
IS  - 0340-6245 (Linking)
VI  - 86
IP  - 6
DP  - 2001 Dec
TI  - Recombinant tissue factor pathway inhibitor prevents lipopolysaccharide-induced 
      systemic hypotension in rats by inhibiting excessive production of nitric oxide.
PG  - 1573-7
AB  - Excessive production of nitric oxide (NO) by the inducible form of NO synthase 
      (iNOS) plays a key role in the development of endotoxin shock. Tumor necrosis 
      factor-alpha (TNF-alpha) induces iNOS, thereby contributing to the development of 
      shock. We recently reported that recombinant tissue factor pathway inhibitor 
      (r-TFPI), an important inhibitor of the extrinsic pathway of the coagulation 
      system, inhibits TNF-alpha production by monocytes. In this study, we 
      investigated whether r-TFPI could ameliorate hypotension by inhibiting excessive 
      production of NO in rats given lipopolysaccharide (LPS). Pretreatment of animals 
      with r-TFPI prevented LPS-induced hypotension. Recombinant TFPI significantly 
      inhibited the increases in both the plasma levels of NO2-/NO3- and lung iNOS 
      activity 3 h after LPS administration. Expression of iNOS mRNA in the lung was 
      also inhibited by intravenous administration of r-TFPI. However, neither 
      DX-9065a, a selective inhibitor of factor Xa, nor an inactive derivative of 
      factor VIIa (DEGR-F.Vlla) that selectively inhibits factor VIIa activity, had any 
      effect on LPS-induced hypotension despite their potent anticoagulant effects. 
      Moreover, neither the plasma levels of NO2-/NO3- nor lung iNOS activity were 
      affected by administration of DX-9065a and DEGR-F.VIIa. These results suggested 
      that r-TFPI ameliorates LPS-induced hypotension by reducing excessive production 
      of NO in rats given LPS and this effect was not attributable to its anticoagulant 
      effects, but to the inhibition of TNF-alpha production.
FAU - Enkhbaatar, P
AU  - Enkhbaatar P
AD  - Department of Laboratory Medicine, Kumamoto University School of Medicine, Japan.
FAU - Okajima, K
AU  - Okajima K
FAU - Uchiba, M
AU  - Uchiba M
FAU - Isobe, H
AU  - Isobe H
FAU - Okabe, H
AU  - Okabe H
LA  - eng
PT  - Journal Article
PL  - Germany
TA  - Thromb Haemost
JT  - Thrombosis and haemostasis
JID - 7608063
RN  - 0 
      ((2S)-2-(4-(((3S)-1-acetimidoyl-3-pyrrolidinyl)oxy)phenyl)-3-(7-amidino-2-naphtyl)propanoic 
      acid)
RN  - 0 (Dansyl Compounds)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Factor Xa Inhibitors)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Lipoproteins)
RN  - 0 (Naphthalenes)
RN  - 0 (Nitrates)
RN  - 0 (Nitrites)
RN  - 0 (Propionates)
RN  - 0 (RNA, Messenger)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (dansyl-glutamyl-glycyl-arginyl-factor VIIa)
RN  - 0 (lipoprotein-associated coagulation inhibitor)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - EC 1.14.13.39 (NOS2 protein, human)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type II)
RN  - EC 1.14.13.39 (Nos2 protein, rat)
RN  - EC 3.4.21.21 (Factor VIIa)
SB  - IM
MH  - Animals
MH  - Dansyl Compounds/pharmacology
MH  - Enzyme Induction/drug effects
MH  - Enzyme Inhibitors/pharmacology
MH  - Factor VIIa/antagonists & inhibitors/pharmacology
MH  - Factor Xa Inhibitors
MH  - Gene Expression Regulation/drug effects
MH  - Humans
MH  - Hypotension/chemically induced/metabolism/*prevention & control
MH  - Lipopolysaccharides/*toxicity
MH  - Lipoproteins/genetics/pharmacology/*therapeutic use
MH  - Lung/drug effects/enzymology
MH  - Male
MH  - Naphthalenes/pharmacology
MH  - Nitrates/blood
MH  - Nitric Oxide/*biosynthesis
MH  - Nitric Oxide Synthase/*antagonists & inhibitors/metabolism
MH  - Nitric Oxide Synthase Type II
MH  - Nitrites/blood
MH  - Propionates/pharmacology
MH  - RNA, Messenger/biosynthesis
MH  - Rats
MH  - Rats, Wistar
MH  - Recombinant Fusion Proteins/pharmacology/therapeutic use
MH  - Respiratory Distress Syndrome/chemically induced/enzymology/prevention & control
MH  - Shock, Septic/metabolism/*prevention & control
MH  - Specific Pathogen-Free Organisms
MH  - Tumor Necrosis Factor-alpha/biosynthesis/genetics/*physiology
EDAT- 2002/01/05 10:00
MHDA- 2002/07/13 10:01
CRDT- 2002/01/05 10:00
PHST- 2002/01/05 10:00 [pubmed]
PHST- 2002/07/13 10:01 [medline]
PHST- 2002/01/05 10:00 [entrez]
AID - 01121573 [pii]
PST - ppublish
SO  - Thromb Haemost. 2001 Dec;86(6):1573-7.