PMID- 17259438
OWN - NLM
STAT- MEDLINE
DCOM- 20070627
LR  - 20200930
IS  - 0363-6135 (Print)
IS  - 0363-6135 (Linking)
VI  - 292
IP  - 5
DP  - 2007 May
TI  - Exercise-induced activation of cardiac sympathetic nerve triggers 
      cardioprotection via redox-sensitive activation of eNOS and upregulation of iNOS.
PG  - H2051-9
AB  - We investigated the mechanism of exercise-induced late cardioprotection against 
      ischemia-reperfusion (I/R) injury. C57BL/6 mice received treadmill exercise (60 
      min/day) for 7 days at a work rate of 60-70% maximal oxygen uptake. Exercise 
      transiently increased oxidative stress and activated endothelial isoform of 
      nitric oxide synthase (eNOS) during exercise and increased expression of 
      inducible isoform of NOS (iNOS) in the heart after 7 days of exercise. The mice 
      were subjected to regional ischemia by 30 min of occlusion of the left coronary 
      artery, followed by 2 h of reperfusion. Infarct size was significantly smaller in 
      the exercised mice. Ablation of cardiac sympathetic nerve by topical application 
      of phenol abolished oxidative stress, activation of eNOS, upregulation of iNOS, 
      and cardioprotection mediated by exercise. Treatment with the antioxidant 
      N-(2-mercaptopropionyl)-glycine during exercise also inhibited activation of 
      eNOS, upregulation of iNOS, and cardioprotection. In eNOS(-/-) mice, 
      exercise-induced oxidative stress was conserved, but upregulation of iNOS and 
      cardioprotection was lost. Exercise did not confer cardioprotection when the iNOS 
      selective inhibitor 1400W was administered just before coronary artery occlusion 
      or when iNOS(-/-) mice were employed. These results suggest that exercise 
      stimulates cardiac sympathetic nerves that provoke redox-sensitive activation of 
      eNOS, leading to upregulation of iNOS, which acts as a mediator of late 
      cardioprotection against I/R injury.
FAU - Akita, Yuzo
AU  - Akita Y
AD  - 2nd Department of Internal Medicine, Division of Cardiology, Kansai Medical 
      University, 10-15 Fumizono-cho, Moriguchi City, 570-8507, Japan.
FAU - Otani, Hajime
AU  - Otani H
FAU - Matsuhisa, Seiji
AU  - Matsuhisa S
FAU - Kyoi, Shiori
AU  - Kyoi S
FAU - Enoki, Chiharu
AU  - Enoki C
FAU - Hattori, Reiji
AU  - Hattori R
FAU - Imamura, Hiroji
AU  - Imamura H
FAU - Kamihata, Hiroshi
AU  - Kamihata H
FAU - Kimura, Yutaka
AU  - Kimura Y
FAU - Iwasaka, Toshiji
AU  - Iwasaka T
LA  - eng
PT  - Journal Article
DEP - 20070126
PL  - United States
TA  - Am J Physiol Heart Circ Physiol
JT  - American journal of physiology. Heart and circulatory physiology
JID - 100901228
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type II)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type III)
RN  - EC 1.14.13.39 (Nos2 protein, mouse)
RN  - EC 1.14.13.39 (Nos3 protein, mouse)
SB  - IM
MH  - Animals
MH  - Enzyme Activation
MH  - Exercise Therapy/*methods
MH  - Male
MH  - Mice
MH  - Mice, Knockout
MH  - Nitric Oxide Synthase Type II/*metabolism
MH  - Nitric Oxide Synthase Type III
MH  - Oxidation-Reduction
MH  - Physical Conditioning, Animal/*methods
MH  - Physical Exertion
MH  - Reperfusion Injury/*physiopathology/*prevention & control
MH  - Sympathetic Nervous System/*physiopathology
MH  - Treatment Outcome
MH  - Up-Regulation/physiology
EDAT- 2007/01/30 09:00
MHDA- 2007/06/28 09:00
CRDT- 2007/01/30 09:00
PHST- 2007/01/30 09:00 [pubmed]
PHST- 2007/06/28 09:00 [medline]
PHST- 2007/01/30 09:00 [entrez]
AID - 01102.2006 [pii]
AID - 10.1152/ajpheart.01102.2006 [doi]
PST - ppublish
SO  - Am J Physiol Heart Circ Physiol. 2007 May;292(5):H2051-9. doi: 
      10.1152/ajpheart.01102.2006. Epub 2007 Jan 26.