PMID- 12045263
OWN - NLM
STAT- MEDLINE
DCOM- 20020701
LR  - 20181113
IS  - 0021-9738 (Print)
IS  - 1558-8238 (Electronic)
IS  - 0021-9738 (Linking)
VI  - 109
IP  - 11
DP  - 2002 Jun
TI  - Cytosolic phospholipase A(2) in hypoxic pulmonary vasoconstriction.
PG  - 1493-500
AB  - Cytosolic phospholipase A(2) (cPLA(2)) releases arachidonic acid (AA) from 
      phospholipids in cell membranes. To assess the role of cPLA(2) in hypoxic 
      pulmonary vasoconstriction (HPV), we measured the increase in left lung pulmonary 
      vascular resistance (LPVR) before and during hypoxia produced by left main stem 
      bronchus occlusion (LMBO) in mice with and without a targeted deletion of the 
      PLA2g4a gene that encodes cPLA(2alpha). LMBO increased LPVR in cPLA(2alpha)(+/+) 
      mice but not in cPLA(2alpha)(-/-) mice. cPLA(2alpha)(+/+) mice were better able 
      to maintain systemic oxygenation during LMBO than were cPLA(2alpha)(-/-) mice. 
      Administration of a cPLA(2) inhibitor, arachidonyl trifluoromethyl ketone, 
      blocked the LMBO-induced increase in LPVR in wild-type mice, while exogenous AA 
      restored HPV in cPLA(2alpha)(-/-) mice. Intravenous angiotensin II infusion 
      increased PVR similarly in cPLA(2alpha)(+/+) and cPLA(2alpha)(-/-) mice. 
      Inhibitors of cyclooxygenase or nitric oxide synthase restored HPV in 
      cPLA(2alpha)(-/-) mice. Breathing 10% oxygen for 3 weeks produced less right 
      ventricular hypertrophy in cPLA(2alpha)(-/-) than in cPLA(2alpha)(+/+) mice, but 
      restored HPV in cPLA(2alpha)(-/-) mice despite the continued absence of cPLA(2) 
      activity. These results indicate that cPLA(2) contributes to the murine pulmonary 
      vasoconstrictor response to hypoxia. Augmenting pulmonary vascular tone restores 
      HPV in the absence of cPLA(2) activity.
FAU - Ichinose, Fumito
AU  - Ichinose F
AD  - Department of Anesthesia and Critical Care, Massachusetts General Hospital, 
      Harvard Medical School, Boston, Massachusetts 02114, USA. 
      ichinose@etherdome.mgh.harvard.edu
FAU - Ullrich, Roman
AU  - Ullrich R
FAU - Sapirstein, Adam
AU  - Sapirstein A
FAU - Jones, Rosemary C
AU  - Jones RC
FAU - Bonventre, Joseph V
AU  - Bonventre JV
FAU - Serhan, Charles N
AU  - Serhan CN
FAU - Bloch, Kenneth D
AU  - Bloch KD
FAU - Zapol, Warren M
AU  - Zapol WM
LA  - eng
GR  - DK-02493/DK/NIDDK NIH HHS/United States
GR  - HL-42397/HL/NHLBI NIH HHS/United States
GR  - P01 DK050305/DK/NIDDK NIH HHS/United States
GR  - P01 DE013499/DE/NIDCR NIH HHS/United States
GR  - R01 HL042397/HL/NHLBI NIH HHS/United States
GR  - DK-50305/DK/NIDDK NIH HHS/United States
GR  - HL-57172/HL/NHLBI NIH HHS/United States
GR  - P01-DE-13499/DE/NIDCR 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  - J Clin Invest
JT  - The Journal of clinical investigation
JID - 7802877
RN  - 0 (Cyclooxygenase Inhibitors)
RN  - 0 (Eicosanoids)
RN  - 0 (Enzyme Inhibitors)
RN  - 11128-99-7 (Angiotensin II)
RN  - EC 3.1.1.32 (Phospholipases A)
RN  - S88TT14065 (Oxygen)
RN  - SY7Q814VUP (Calcium)
RN  - V55S2QJN2X (NG-Nitroarginine Methyl Ester)
RN  - XXE1CET956 (Indomethacin)
SB  - IM
MH  - Angiotensin II/metabolism
MH  - Animals
MH  - Calcium/metabolism
MH  - Cell Membrane/enzymology
MH  - Cyclooxygenase Inhibitors/pharmacology
MH  - Cytosol/*enzymology
MH  - Eicosanoids/metabolism
MH  - Enzyme Inhibitors/pharmacology
MH  - Gas Chromatography-Mass Spectrometry
MH  - Genotype
MH  - Hypoxia
MH  - Indomethacin/pharmacology
MH  - Lung/*enzymology
MH  - Mice
MH  - NG-Nitroarginine Methyl Ester/pharmacology
MH  - Oxygen/metabolism
MH  - Phospholipases A/*metabolism/*physiology
MH  - Time Factors
MH  - Vasoconstriction
PMC - PMC150993
EDAT- 2002/06/05 10:00
MHDA- 2002/07/02 10:01
PMCR- 2002/06/01
CRDT- 2002/06/05 10:00
PHST- 2002/06/05 10:00 [pubmed]
PHST- 2002/07/02 10:01 [medline]
PHST- 2002/06/05 10:00 [entrez]
PHST- 2002/06/01 00:00 [pmc-release]
AID - 14294 [pii]
AID - 10.1172/JCI14294 [doi]
PST - ppublish
SO  - J Clin Invest. 2002 Jun;109(11):1493-500. doi: 10.1172/JCI14294.