PMID- 11325876
OWN - NLM
STAT- MEDLINE
DCOM- 20010719
LR  - 20190706
IS  - 1524-4571 (Electronic)
IS  - 0009-7330 (Linking)
VI  - 88
IP  - 8
DP  - 2001 Apr 27
TI  - Attenuation of hypoxic pulmonary vasoconstriction by endotoxemia requires 
      5-lipoxygenase in mice.
PG  - 832-8
AB  - Sepsis and endotoxemia impair hypoxic pulmonary vasoconstriction (HPV), thereby 
      reducing systemic oxygenation. To assess the role of leukotrienes (LTs) in the 
      attenuation of HPV during endotoxemia, the increase in left lung pulmonary 
      vascular resistance (LPVR) before and during left mainstem bronchus occlusion 
      (LMBO) was measured in mice with and without a deletion of the gene encoding 
      5-lipoxygenase (5-LO). LMBO increased the LPVR equally in saline-challenged 
      wild-type and 5-LO-deficient mice (96+/-20% and 94+/-19%, respectively). 
      Twenty-two hours after challenge with Escherichia coli endotoxin, the ability of 
      LMBO to increase LPVR was markedly impaired in wild-type mice (27+/-7%; P<0.05) 
      but not in 5-LO-deficient mice (72+/-9%) or in wild-type mice pretreated with 
      MK886, an inhibitor of 5-LO activity (76+/-10%). Compared with wild-type mice, 
      endotoxin-induced disruption of lung structures and inflammatory cell influx in 
      the lung were markedly attenuated in 5-LO-deficient mice. Administration of 
      MK571, a selective cysteinyl LT(1) receptor antagonist, 1 hour before endotoxin 
      challenge preserved HPV and attenuated pulmonary injury in wild-type mice but did 
      not prevent the endotoxin-induced increase in pulmonary myeloperoxidase activity. 
      Taken together, these findings demonstrate that a 5-LO product, most likely a 
      cysteinyl LT, contributes to the attenuation of HPV and to pulmonary injury after 
      challenge with endotoxin.
FAU - Ichinose, F
AU  - Ichinose F
AD  - Department of Anesthesia, Massachusetts General Hospital, Harvard Medical School, 
      Boston, Massachusetts, USA. ichinose@etherdome.mgh.harvard.edu
FAU - Zapol, W M
AU  - Zapol WM
FAU - Sapirstein, A
AU  - Sapirstein A
FAU - Ullrich, R
AU  - Ullrich R
FAU - Tager, A M
AU  - Tager AM
FAU - Coggins, K
AU  - Coggins K
FAU - Jones, R
AU  - Jones R
FAU - Bloch, K D
AU  - Bloch KD
LA  - eng
GR  - HL-42397/HL/NHLBI NIH HHS/United States
GR  - HL-55377/HL/NHLBI NIH HHS/United States
GR  - P01-DK38108/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Circ Res
JT  - Circulation research
JID - 0047103
RN  - 0 (Endotoxins)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Leukotriene Antagonists)
RN  - 0 (Leukotrienes)
RN  - 0 (Lipoxygenase Inhibitors)
RN  - 0 (Membrane Proteins)
RN  - 0 (Receptors, Leukotriene)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - 67924-63-4 (endotoxin, Escherichia coli)
RN  - AJT72OTM42 (cysteinyl leukotriene receptor 2)
RN  - EC 1.11.1.7 (Peroxidase)
RN  - EC 1.13.11.34 (Arachidonate 5-Lipoxygenase)
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, mouse)
RN  - LRF7RW46ID (leukotriene D4 receptor)
SB  - IM
MH  - Administration, Inhalation
MH  - Animals
MH  - Arachidonate 5-Lipoxygenase/deficiency/*metabolism
MH  - Bronchoalveolar Lavage Fluid/chemistry
MH  - Disease Models, Animal
MH  - Endotoxemia/chemically induced/complications/*metabolism
MH  - Endotoxins/pharmacology
MH  - Enzyme Inhibitors/pharmacology
MH  - Hemodynamics/drug effects
MH  - Hypoxia/complications/enzymology/*physiopathology
MH  - Leukocyte Count
MH  - Leukotriene Antagonists/pharmacology
MH  - Leukotrienes/analysis
MH  - Lipoxygenase Inhibitors/pharmacology
MH  - Lung/blood supply/drug effects/pathology
MH  - *Membrane Proteins
MH  - Mice
MH  - Mice, Mutant Strains
MH  - Nitric Oxide/administration & dosage
MH  - Nitric Oxide Synthase/metabolism
MH  - Nitric Oxide Synthase Type II
MH  - Peroxidase/metabolism
MH  - Pulmonary Alveoli/blood supply/metabolism
MH  - *Pulmonary Circulation/drug effects/physiology
MH  - *Receptors, Leukotriene
MH  - *Vascular Resistance/drug effects/physiology
MH  - *Vasoconstriction/drug effects/physiology
EDAT- 2001/04/28 10:00
MHDA- 2001/07/20 10:01
CRDT- 2001/04/28 10:00
PHST- 2001/04/28 10:00 [pubmed]
PHST- 2001/07/20 10:01 [medline]
PHST- 2001/04/28 10:00 [entrez]
AID - 10.1161/hh0801.089177 [doi]
PST - ppublish
SO  - Circ Res. 2001 Apr 27;88(8):832-8. doi: 10.1161/hh0801.089177.