PMID- 27313889
OWN - NLM
STAT- MEDLINE
DCOM- 20170309
LR  - 20181113
IS  - 2090-1844 (Electronic)
IS  - 2090-1836 (Print)
IS  - 2090-1844 (Linking)
VI  - 2016
DP  - 2016
TI  - Long-Term Chronic Intermittent Hypobaric Hypoxia in Rats Causes an Imbalance in 
      the Asymmetric Dimethylarginine/Nitric Oxide Pathway and ROS Activity: A Possible 
      Synergistic Mechanism for Altitude Pulmonary Hypertension?
PG  - 6578578
LID - 10.1155/2016/6578578 [doi]
LID - 6578578
AB  - Chronic intermittent hypoxia (CIH) and chronic hypoxia (CH) are associated with 
      high-altitude pulmonary hypertension (HAPH). Asymmetric dimethylarginine (ADMA), 
      a NO synthase (NOS) inhibitor, may contribute to HAPH. This study assessed 
      changes in the ADMA/NO pathway and the underlying mechanisms in rat lungs 
      following exposure to CIH or CH simulated in a hypobaric chamber at 428 Torr. 
      Twenty-four adult Wistar rats were randomly assigned to three groups: CIH2x2 (2 
      days of hypoxia/2 days of normoxia), CH, and NX (permanent normoxia), for 30 
      days. All analyses were performed in whole lung tissue. L-Arginine and ADMA were 
      analyzed using LC-MS/MS. Under both hypoxic conditions right ventricular 
      hypertrophy was observed (p < 0.01) and endothelial NOS mRNA increased (p < 
      0.001), but the phosphorylated/nonphosphorylated vasodilator-stimulated 
      phosphoprotein (VASP) ratio was unchanged. ADMA increased (p < 0.001), whereas 
      dimethylarginine dimethylaminohydrolase (DDAH) activity decreased only under CH 
      (p < 0.05). Although arginase activity increased (p < 0.001) and L-arginine 
      exhibited no changes, the L-arginine/ADMA ratio decreased significantly (p < 
      0.001). Moreover, NOX4 expression increased only under CH (p < 0.01), but 
      malondialdehyde (MDA) increased (up to 2-fold) equally in CIH2x2 and CH (p < 
      0.001). Our results suggest that ADMA and oxidative stress likely reduce NO 
      bioavailability under altitude hypoxia, which implies greater pulmonary vascular 
      reactivity and tone, despite the more subdued effects observed under CIH.
FAU - Luneburg, Nicole
AU  - Luneburg N
AD  - Department of Clinical Pharmacology and Toxicology, University Medical Center 
      Hamburg-Eppendorf, 20246 Hamburg, Germany.
FAU - Siques, Patricia
AU  - Siques P
AD  - Institute of Health Studies, Arturo Prat University, Iquique, Chile.
FAU - Brito, Julio
AU  - Brito J
AD  - Institute of Health Studies, Arturo Prat University, Iquique, Chile.
FAU - Arriaza, Karem
AU  - Arriaza K
AD  - Institute of Health Studies, Arturo Prat University, Iquique, Chile.
FAU - Pena, Eduardo
AU  - Pena E
AD  - Institute of Health Studies, Arturo Prat University, Iquique, Chile.
FAU - Klose, Hans
AU  - Klose H
AD  - Department of Pneumology, University Medical Center Hamburg-Eppendorf, 20246 
      Hamburg, Germany.
FAU - Leon-Velarde, Fabiola
AU  - Leon-Velarde F
AD  - Department of Biological and Physiological Sciences, Faculty of Sciences and 
      Philosophy/IIA, Cayetano Heredia University, Lima, Peru.
FAU - Boger, Rainer H
AU  - Boger RH
AD  - Department of Clinical Pharmacology and Toxicology, University Medical Center 
      Hamburg-Eppendorf, 20246 Hamburg, Germany.
LA  - eng
PT  - Journal Article
DEP - 20160530
PL  - Egypt
TA  - Pulm Med
JT  - Pulmonary medicine
JID - 101558762
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - 63CV1GEK3Y (N,N-dimethylarginine)
RN  - 94ZLA3W45F (Arginine)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase)
RN  - EC 3.5.- (Amidohydrolases)
RN  - EC 3.5.3.18 (dimethylargininase)
RN  - Pulmonary edema of mountaineers
SB  - IM
MH  - *Altitude Sickness/metabolism/physiopathology
MH  - Amidohydrolases/metabolism
MH  - Animals
MH  - Arginine/*analogs & derivatives/metabolism
MH  - Disease Models, Animal
MH  - *Hypertension, Pulmonary/metabolism/physiopathology
MH  - *Hypoxia/metabolism/physiopathology
MH  - *Lung/blood supply/metabolism/physiopathology
MH  - Male
MH  - Nitric Oxide/*metabolism
MH  - Nitric Oxide Synthase/antagonists & inhibitors
MH  - Oxidative Stress
MH  - Pulmonary Circulation
MH  - Rats
MH  - Rats, Wistar
MH  - Signal Transduction
MH  - Time Factors
MH  - Vascular Resistance
PMC - PMC4904121
EDAT- 2016/06/18 06:00
MHDA- 2017/03/10 06:00
PMCR- 2016/05/30
CRDT- 2016/06/18 06:00
PHST- 2016/03/07 00:00 [received]
PHST- 2016/05/08 00:00 [accepted]
PHST- 2016/06/18 06:00 [entrez]
PHST- 2016/06/18 06:00 [pubmed]
PHST- 2017/03/10 06:00 [medline]
PHST- 2016/05/30 00:00 [pmc-release]
AID - 10.1155/2016/6578578 [doi]
PST - ppublish
SO  - Pulm Med. 2016;2016:6578578. doi: 10.1155/2016/6578578. Epub 2016 May 30.