PMID- 17720871
OWN - NLM
STAT- MEDLINE
DCOM- 20071220
LR  - 20201209
IS  - 1040-0605 (Print)
IS  - 1040-0605 (Linking)
VI  - 293
IP  - 5
DP  - 2007 Nov
TI  - Congenital NOS2 deficiency prevents impairment of hypoxic pulmonary 
      vasoconstriction in murine ventilator-induced lung injury.
PG  - L1300-5
AB  - Hypoxic pulmonary vasoconstriction (HPV) preserves systemic arterial oxygenation 
      during lung injury by diverting blood flow away from poorly ventilated lung 
      regions. Ventilator-induced lung injury (VILI) is characterized by pulmonary 
      inflammation, lung edema, and impaired HPV leading to systemic hypoxemia. 
      Studying mice congenitally deficient in inducible nitric oxide synthase (NOS2) 
      and wild-type mice treated with a selective NOS2 inhibitor, 
      L-N(6)-(1-iminoethyl)lysine (L-NIL), we investigated the contribution of NOS2 to 
      the impairment of HPV in anesthetized mice subjected to 6 h of either high tidal 
      volume (HV(T)) or low tidal volume (LV(T)) ventilation. HPV was estimated by 
      measuring the changes of left lung pulmonary vascular resistance (LPVR) in 
      response to left mainstem bronchus occlusion (LMBO). LMBO increased the LPVR 
      similarly in wild-type, NOS2(-/-), and wild-type mice treated with L-NIL 30 min 
      before commencing 6 h of LV(T) ventilation (96% +/- 30%, 103% +/- 33%, and 80% 
      +/- 16%, respectively, means +/- SD). HPV was impaired in wild-type mice 
      subjected to 6 h of HV(T) ventilation (23% +/- 16%). In contrast, HPV was 
      preserved after 6 h of HV(T) ventilation in NOS2(-/-) and wild-type mice treated 
      with L-NIL either 30 min before or 6 h after commencing HV(T) ventilation (66% 
      +/- 22%, 82% +/- 29%, and 85% +/- 16%, respectively). After 6 h of HV(T) 
      ventilation and LMBO, systemic arterial oxygen tension was higher in NOS2(-/-) 
      than in wild-type mice (192 +/- 11 vs. 171 +/- 17 mmHg; P < 0.05). We conclude 
      that either congenital NOS2 deficiency or selective inhibition of NOS2 protects 
      mice from the impairment of HPV occurring after 6 h of HV(T) ventilation.
FAU - Liu, Rong
AU  - Liu R
AD  - Dept. of Anesthesia and Critical Care, Massachusetts General Hospital, Harvard 
      Medical School, Boston, Massachusetts 02114, USA.
FAU - Hotta, Yukako
AU  - Hotta Y
FAU - Graveline, Amanda R
AU  - Graveline AR
FAU - Evgenov, Oleg V
AU  - Evgenov OV
FAU - Buys, Emmanuel S
AU  - Buys ES
FAU - Bloch, Kenneth D
AU  - Bloch KD
FAU - Ichinose, Fumito
AU  - Ichinose F
FAU - Zapol, Warren M
AU  - Zapol WM
LA  - eng
GR  - HL-42397/HL/NHLBI NIH HHS/United States
GR  - HL-71987/HL/NHLBI NIH HHS/United States
GR  - HL-74352/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20070824
PL  - United States
TA  - Am J Physiol Lung Cell Mol Physiol
JT  - American journal of physiology. Lung cellular and molecular physiology
JID - 100901229
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (N(6)-(1-iminoethyl)lysine)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type II)
RN  - EC 1.14.13.39 (Nos2 protein, mouse)
RN  - K3Z4F929H6 (Lysine)
SB  - IM
MH  - Animals
MH  - Bronchoconstriction
MH  - Enzyme Inhibitors/pharmacology
MH  - Hypoxia/physiopathology
MH  - Lung/*blood supply
MH  - Lysine/analogs & derivatives/pharmacology
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Nitric Oxide Synthase Type II/*deficiency/genetics
MH  - Pulmonary Artery
MH  - *Pulmonary Ventilation
MH  - Respiratory Distress Syndrome/*etiology
MH  - Respiratory Insufficiency/enzymology/*prevention & control
MH  - Vascular Resistance
MH  - *Vasoconstriction
MH  - Ventilators, Mechanical/*adverse effects
EDAT- 2007/08/28 09:00
MHDA- 2007/12/21 09:00
CRDT- 2007/08/28 09:00
PHST- 2007/08/28 09:00 [pubmed]
PHST- 2007/12/21 09:00 [medline]
PHST- 2007/08/28 09:00 [entrez]
AID - 00396.2006 [pii]
AID - 10.1152/ajplung.00396.2006 [doi]
PST - ppublish
SO  - Am J Physiol Lung Cell Mol Physiol. 2007 Nov;293(5):L1300-5. doi: 
      10.1152/ajplung.00396.2006. Epub 2007 Aug 24.