PMID- 20804862
OWN - NLM
STAT- MEDLINE
DCOM- 20110315
LR  - 20220331
IS  - 1878-1519 (Electronic)
IS  - 1569-9048 (Print)
IS  - 1569-9048 (Linking)
VI  - 174
IP  - 3
DP  - 2010 Dec 31
TI  - Mitochondrial oxidant stress increases PDE5 activity in persistent pulmonary 
      hypertension of the newborn.
PG  - 272-81
LID - 10.1016/j.resp.2010.08.018 [doi]
AB  - In the pulmonary vasculature, phosphodiesterase-5 (PDE5) degrades cGMP and 
      inhibits nitric oxide-mediated, cGMP-dependent vasorelaxation. We previously 
      reported that ventilation with 100% O2 increased PDE5 activity in pulmonary 
      arteries (PAs) of pulmonary hypertension lambs (PPHN) more than in control lambs. 
      In the present study, PA smooth muscle cells (PASMCs) from PPHN lambs had 
      increased basal PDE5 activity, decreased cGMP-responsiveness to NO, and increased 
      mitochondrial matrix oxidant stress compared to control PASMC. Hyperoxia (24 h) 
      increased PDE5 activity and mitochondrial matrix oxidant stress above baseline to 
      a similar degree in PPHN and control PASMC. Mitochondrially targeted catalase 
      decreased PDE5 activity at baseline and after hyperoxia in PPHN PASMC. Similarly, 
      catalase treatment of PPHN lambs ventilated with 100% O2 decreased PDE5 activity 
      and increased cGMP in PA. We conclude that baseline PDE5 activity and oxidative 
      stress is increased in PPHN PASMC, and scavenging H2O2 is sufficient to block 
      oxidant-mediated increases in PDE5 activity in PPHN.
CI  - Copyright (c) 2010 Elsevier B.V. All rights reserved.
FAU - Farrow, Kathryn N
AU  - Farrow KN
AD  - Department of Pediatrics, Northwestern University, Chicago, IL 60611, United 
      States. k-farrow@northwestern.edu
FAU - Wedgwood, Stephen
AU  - Wedgwood S
FAU - Lee, Keng Jin
AU  - Lee KJ
FAU - Czech, Lyubov
AU  - Czech L
FAU - Gugino, Sylvia F
AU  - Gugino SF
FAU - Lakshminrusimha, Satyan
AU  - Lakshminrusimha S
FAU - Schumacker, Paul T
AU  - Schumacker PT
FAU - Steinhorn, Robin H
AU  - Steinhorn RH
LA  - eng
GR  - R01 HL054705-13/HL/NHLBI NIH HHS/United States
GR  - HL086715/HL/NHLBI NIH HHS/United States
GR  - R29 HL054705/HL/NHLBI NIH HHS/United States
GR  - R01 HL079650/HL/NHLBI NIH HHS/United States
GR  - K08 HL086715-03/HL/NHLBI NIH HHS/United States
GR  - R01 HL035440/HL/NHLBI NIH HHS/United States
GR  - R01 HL054705/HL/NHLBI NIH HHS/United States
GR  - R01 HL079650-04/HL/NHLBI NIH HHS/United States
GR  - K08 HL086715/HL/NHLBI NIH HHS/United States
GR  - HL079650/HL/NHLBI NIH HHS/United States
GR  - HL54705/HL/NHLBI NIH HHS/United States
GR  - R01 HL054705-14/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20100906
PL  - Netherlands
TA  - Respir Physiol Neurobiol
JT  - Respiratory physiology & neurobiology
JID - 101140022
RN  - 0 (Reactive Oxygen Species)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - 3WJQ0SDW1A (Polyethylene Glycols)
RN  - EC 1.11.1.6 (Catalase)
RN  - H2D2X058MU (Cyclic GMP)
RN  - S88TT14065 (Oxygen)
SB  - IM
MH  - Animals
MH  - Animals, Newborn
MH  - Catalase/metabolism/pharmacology
MH  - Cells, Cultured
MH  - Cyclic GMP/metabolism
MH  - Disease Models, Animal
MH  - Embryo, Mammalian
MH  - Female
MH  - Gene Expression Regulation/drug effects
MH  - Goats
MH  - Humans
MH  - Immunoassay/methods
MH  - Infant, Newborn
MH  - Mitochondria/drug effects/*metabolism/ultrastructure
MH  - Myocytes, Smooth Muscle/drug effects/*metabolism
MH  - Nitric Oxide/pharmacology
MH  - Oxidative Stress/*physiology
MH  - Oxygen/pharmacology
MH  - Persistent Fetal Circulation Syndrome/*metabolism
MH  - Polyethylene Glycols/pharmacology
MH  - Pregnancy
MH  - Pulmonary Artery/cytology
MH  - Reactive Oxygen Species/metabolism
PMC - PMC2991478
MID - NIHMS234101
EDAT- 2010/09/02 06:00
MHDA- 2011/03/16 06:00
PMCR- 2011/12/31
CRDT- 2010/09/01 06:00
PHST- 2010/06/29 00:00 [received]
PHST- 2010/08/21 00:00 [revised]
PHST- 2010/08/23 00:00 [accepted]
PHST- 2010/09/01 06:00 [entrez]
PHST- 2010/09/02 06:00 [pubmed]
PHST- 2011/03/16 06:00 [medline]
PHST- 2011/12/31 00:00 [pmc-release]
AID - S1569-9048(10)00322-8 [pii]
AID - 10.1016/j.resp.2010.08.018 [doi]
PST - ppublish
SO  - Respir Physiol Neurobiol. 2010 Dec 31;174(3):272-81. doi: 
      10.1016/j.resp.2010.08.018. Epub 2010 Sep 6.