PMID- 10562304
OWN - NLM
STAT- MEDLINE
DCOM- 19991209
LR  - 20181113
IS  - 0021-9738 (Print)
IS  - 0021-9738 (Linking)
VI  - 104
IP  - 10
DP  - 1999 Nov
TI  - Hypoxic pulmonary blood flow redistribution and arterial oxygenation in 
      endotoxin-challenged NOS2-deficient mice.
PG  - 1421-9
AB  - Sepsis and endotoxemia impair hypoxic pulmonary vasoconstriction (HPV), thereby 
      reducing arterial oxygenation and enhancing hypoxemia. Endotoxin induces nitric 
      oxide (NO) production by NO synthase 2 (NOS2). To assess the role of NO and NOS2 
      in the impairment of HPV during endotoxemia, we measured in vivo the distribution 
      of total pulmonary blood flow (QPA) between the right (QRPA) and left (QLPA) 
      pulmonary arteries before and after left mainstem bronchus occlusion (LMBO) in 
      mice with and without a congenital deficiency of NOS2. LMBO reduced QLPA/QPA 
      equally in saline-treated wild-type and NOS2-deficient mice. However, prior 
      challenge with Escherichia coli endotoxin markedly impaired the ability of LMBO 
      to reduce QLPA/QPA in wild-type, but not in NOS2-deficient, mice. After endotoxin 
      challenge and LMBO, systemic oxygenation was impaired to a greater extent in 
      wild-type than in NOS2-deficient mice. When administered shortly after endotoxin 
      treatment, the selective NOS2 inhibitor L-NIL preserved HPV in wild-type mice. 
      High concentrations of inhaled NO attenuated HPV in NOS2-deficient mice 
      challenged with endotoxin. These findings demonstrate that increased pulmonary NO 
      levels (produced by NOS2 or inhaled at high levels from exogenous sources) are 
      necessary during the septic process to impair HPV, ventilation/perfusion matching 
      and arterial oxygenation in a murine sepsis model.
FAU - Ullrich, R
AU  - Ullrich R
AD  - Department of Anesthesia and Critical Care, Massachusetts General Hospital, 
      Harvard Medical School, Boston, Massachusetts 02114, USA.
FAU - Bloch, K D
AU  - Bloch KD
FAU - Ichinose, F
AU  - Ichinose F
FAU - Steudel, W
AU  - Steudel W
FAU - Zapol, W M
AU  - Zapol WM
LA  - eng
GR  - R01 HL042397/HL/NHLBI NIH HHS/United States
GR  - HL42397/HL/NHLBI NIH HHS/United States
GR  - HL55377/HL/NHLBI 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 (Endotoxins)
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  - S88TT14065 (Oxygen)
SB  - IM
MH  - Animals
MH  - Blood Pressure/drug effects
MH  - Bronchi/*physiology/physiopathology
MH  - Crosses, Genetic
MH  - Endotoxins/*toxicity
MH  - Escherichia coli
MH  - Female
MH  - Heart Rate/drug effects
MH  - Hypoxia/*physiopathology
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Inbred Strains
MH  - Mice, Mutant Strains
MH  - Nitric Oxide Synthase/*deficiency/metabolism
MH  - Nitric Oxide Synthase Type II
MH  - Oxygen/*blood
MH  - Pulmonary Artery/drug effects/*physiology/physiopathology
MH  - Pulmonary Circulation/*physiology
MH  - Regional Blood Flow
MH  - Vasoconstriction/drug effects/physiology
PMC - PMC409836
EDAT- 1999/11/24 00:00
MHDA- 1999/11/24 00:01
PMCR- 1999/11/15
CRDT- 1999/11/24 00:00
PHST- 1999/11/24 00:00 [pubmed]
PHST- 1999/11/24 00:01 [medline]
PHST- 1999/11/24 00:00 [entrez]
PHST- 1999/11/15 00:00 [pmc-release]
AID - 06590 [pii]
AID - 10.1172/JCI6590 [doi]
PST - ppublish
SO  - J Clin Invest. 1999 Nov;104(10):1421-9. doi: 10.1172/JCI6590.