PMID- 28302706
OWN - NLM
STAT- MEDLINE
DCOM- 20180622
LR  - 20181113
IS  - 1522-1601 (Electronic)
IS  - 8750-7587 (Print)
IS  - 0161-7567 (Linking)
VI  - 123
IP  - 4
DP  - 2017 Oct 1
TI  - Acclimatization of the systemic microcirculation to alveolar hypoxia is mediated 
      by an iNOS-dependent increase in nitric oxide availability.
PG  - 974-982
LID - 10.1152/japplphysiol.00322.2016 [doi]
AB  - Rats breathing 10% O(2) show a rapid and widespread systemic microvascular 
      inflammation that results from nitric oxide (NO) depletion secondary to increased 
      reactive O(2) species (ROS) generation. The inflammation eventually resolves, and 
      the microcirculation becomes resistant to more severe hypoxia. These experiments 
      were directed to determine the mechanisms underlying this microvascular 
      acclimatization process. Intravital microscopy of the mesentery showed that after 
      3 wk of hypoxia (barometric pressure ~380 Torr; partial pressure of inspired O(2) 
      ~68-70 Torr), rats showed no evidence of inflammation; however, treatment with 
      the inducible NO synthase (iNOS) inhibitor L-N(6)-(1-iminoethyl) lysine 
      dihydrochloride led to ROS generation, leukocyte-endothelial adherence and 
      emigration, and increased vascular permeability. Mast cells harvested from 
      normoxic rats underwent degranulation when exposed in vitro to monocyte 
      chemoattractant protein-1 (MCP-1), the proximate mediator of mast cell 
      degranulation in acute hypoxia. Mast cell degranulation by MCP-1 was prevented by 
      the NO donor spermine-NONOate. MCP-1 did not induce degranulation of mast cells 
      harvested from 6-day hypoxic rats; however, pretreatment with either the general 
      NOS inhibitor L-NG-monomethyl arginine citrate or the selective iNOS inhibitor 
      N-[3-(aminomethyl) benzyl] acetamidine restored the effect of MCP-1. iNOS was 
      demonstrated in mast cells and alveolar macrophages of acclimatized rats. Nitrate 
      + nitrite plasma levels decreased significantly in acute hypoxia and were 
      restored after 6 days of acclimatization. The results support the hypothesis that 
      the microvascular acclimatization to hypoxia results from the restoration of the 
      ROS/NO balance mediated by iNOS expression at key sites in the inflammatory 
      cascade.NEW & NOTEWORTHY The study shows that the systemic inflammation of acute 
      hypoxia resolves via an inducible nitric oxide (NO) synthase-induced restoration 
      of the reactive O(2) species/NO balance in the systemic microcirculation. It is 
      proposed that the acute systemic inflammation may represent the first step of the 
      microvascular acclimatization process.
CI  - Copyright (c) 2017 the American Physiological Society.
FAU - Casillan, Alfred J
AU  - Casillan AJ
AD  - Department of Molecular and Integrative Physiology, University of Kansas Medical 
      Center, Kansas City, Kansas; and.
FAU - Chao, Jie
AU  - Chao J
AUID- ORCID: 0000-0002-7800-3557
AD  - Department of Molecular and Integrative Physiology, University of Kansas Medical 
      Center, Kansas City, Kansas; and.
FAU - Wood, John G
AU  - Wood JG
AD  - Department of Molecular and Integrative Physiology, University of Kansas Medical 
      Center, Kansas City, Kansas; and.
AD  - Department of Surgery, University of Kansas Medical Center, Kansas City, Kansas.
FAU - Gonzalez, Norberto C
AU  - Gonzalez NC
AD  - Department of Molecular and Integrative Physiology, University of Kansas Medical 
      Center, Kansas City, Kansas; and ngonzale@kumc.edu.
LA  - eng
PT  - Journal Article
DEP - 20170316
PL  - United States
TA  - J Appl Physiol (1985)
JT  - Journal of applied physiology (Bethesda, Md. : 1985)
JID - 8502536
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type II)
SB  - IM
MH  - Acclimatization/*physiology
MH  - Animals
MH  - Hypoxia/*metabolism
MH  - Macrophages, Alveolar/metabolism
MH  - Male
MH  - Mast Cells/metabolism
MH  - Microcirculation/*physiology
MH  - Nitric Oxide/*metabolism
MH  - Nitric Oxide Synthase Type II/*metabolism
MH  - Pulmonary Alveoli/*metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
PMC - PMC5668455
OTO - NOTNLM
OT  - ROS/NO balance
OT  - acclimatization
OT  - alveolar hypoxia
OT  - iNOS
OT  - inflammation
EDAT- 2017/03/18 06:00
MHDA- 2018/06/23 06:00
PMCR- 2018/10/01
CRDT- 2017/03/18 06:00
PHST- 2016/04/06 00:00 [received]
PHST- 2017/02/15 00:00 [revised]
PHST- 2017/03/12 00:00 [accepted]
PHST- 2017/03/18 06:00 [pubmed]
PHST- 2018/06/23 06:00 [medline]
PHST- 2017/03/18 06:00 [entrez]
PHST- 2018/10/01 00:00 [pmc-release]
AID - japplphysiol.00322.2016 [pii]
AID - JAPPL-00322-2016 [pii]
AID - 10.1152/japplphysiol.00322.2016 [doi]
PST - ppublish
SO  - J Appl Physiol (1985). 2017 Oct 1;123(4):974-982. doi: 
      10.1152/japplphysiol.00322.2016. Epub 2017 Mar 16.