PMID- 15939832
OWN - NLM
STAT- MEDLINE
DCOM- 20060125
LR  - 20161019
IS  - 1524-4539 (Electronic)
IS  - 0009-7322 (Linking)
VI  - 111
IP  - 22
DP  - 2005 Jun 7
TI  - Endothelium-derived nitric oxide regulates postischemic myocardial oxygenation 
      and oxygen consumption by modulation of mitochondrial electron transport.
PG  - 2966-72
AB  - BACKGROUND: Nitric oxide (NO) production is increased in postischemic myocardium, 
      and NO can control mitochondrial oxygen consumption in vitro. Therefore, we 
      investigated the role of endothelial NO synthase (eNOS)-derived NO on in vivo 
      regulation of oxygen consumption in the postischemic heart. METHODS AND RESULTS: 
      Mice were subjected to 30 minutes of coronary ligation followed by 60 minutes of 
      reperfusion. Myocardial oxygen tension (Po2) was monitored by electron 
      paramagnetic resonance oximetry. In wild-type, N-nitro-L-arginine methyl ester 
      (L-NAME)-treated (with 1 mg/mL in drinking water), and eNOS knockout (eNOS-/-) 
      mice, no difference was observed among baseline myocardial Po2 values (8.6+/-0.7, 
      10.0+/-1.2, and 10.1+/-1.2 mm Hg, respectively) or those measured at 30 minutes 
      of ischemia (1.4+/-0.6, 2.3+/-0.9, and 3.1+/-1.4 mm Hg, respectively). After 
      reperfusion, myocardial Po2 increased markedly (P<0.001 versus baseline in each 
      group) but was much lower in L-NAME-treated and eNOS-/- mice (17.4+/-1.6 and 
      20.4+/-1.9 mm Hg) than in wild-type mice (46.5+/-1.7 mm Hg; P<0.001). A transient 
      peak of myocardial Po2 was observed at early reperfusion in wild-type mice. No 
      reactive hyperemia was observed during early reperfusion. Endothelial NO 
      decreased the rate-pressure product (P<0.05), upregulated cytochrome c oxidase 
      (CcO) mRNA expression (P<0.01) with no change in CcO activity, and inhibited NADH 
      dehydrogenase (NADH-DH) activity (P<0.01) without alteration of NADH-DH mRNA 
      expression. Peroxynitrite-mediated tyrosine nitration was higher in hearts from 
      wild-type mice than in eNOS-/- or L-NAME-treated hearts. CONCLUSIONS: 
      eNOS-derived NO markedly suppresses in vivo O2 consumption in the postischemic 
      heart through modulation of mitochondrial respiration based on alterations in 
      enzyme activity and mRNA expression of NADH-DH and CcO. The marked myocardial 
      hyperoxygenation in reperfused myocardium may be a critical factor that triggers 
      postischemic remodeling.
FAU - Zhao, Xue
AU  - Zhao X
AD  - Center for Biomedical EPR Spectroscopy and Imaging, the Davis Heart and Lung 
      Research Institute, and the Division of Cardiovascular Medicine, Department of 
      Internal Medicine, The Ohio State University College of Medicine, Columbus, Ohio, 
      USA.
FAU - He, Guanglong
AU  - He G
FAU - Chen, Yeong-Renn
AU  - Chen YR
FAU - Pandian, Ramasamy P
AU  - Pandian RP
FAU - Kuppusamy, Periannan
AU  - Kuppusamy P
FAU - Zweier, Jay L
AU  - Zweier JL
LA  - eng
GR  - K22 ES011031/ES/NIEHS NIH HHS/United States
GR  - HL38324/HL/NHLBI NIH HHS/United States
GR  - HL63744/HL/NHLBI NIH HHS/United States
GR  - HL65608/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Circulation
JT  - Circulation
JID - 0147763
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - 3604-79-3 (3-nitrotyrosine)
RN  - 42HK56048U (Tyrosine)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type III)
RN  - EC 1.6.99.3 (NADH Dehydrogenase)
RN  - EC 1.9.3.1 (Electron Transport Complex IV)
RN  - S88TT14065 (Oxygen)
SB  - IM
MH  - Animals
MH  - *Cell Respiration
MH  - Disease Models, Animal
MH  - Electron Transport Complex IV/genetics
MH  - Male
MH  - Mice
MH  - Mice, Knockout
MH  - Myocardial Ischemia/enzymology/*metabolism/pathology
MH  - NADH Dehydrogenase/antagonists & inhibitors
MH  - Nitric Oxide/biosynthesis/*physiology
MH  - Nitric Oxide Synthase Type III/deficiency/*metabolism
MH  - Oximetry
MH  - Oxygen/metabolism
MH  - *Oxygen Consumption
MH  - Tyrosine/analogs & derivatives/analysis
MH  - Up-Regulation
EDAT- 2005/06/09 09:00
MHDA- 2006/01/26 09:00
CRDT- 2005/06/09 09:00
PHST- 2005/06/09 09:00 [pubmed]
PHST- 2006/01/26 09:00 [medline]
PHST- 2005/06/09 09:00 [entrez]
AID - 111/22/2966 [pii]
AID - 10.1161/CIRCULATIONAHA.104.527226 [doi]
PST - ppublish
SO  - Circulation. 2005 Jun 7;111(22):2966-72. doi: 10.1161/CIRCULATIONAHA.104.527226.