PMID- 25681423
OWN - NLM
STAT- MEDLINE
DCOM- 20151231
LR  - 20200930
IS  - 1522-1539 (Electronic)
IS  - 0363-6135 (Linking)
VI  - 308
IP  - 8
DP  - 2015 Apr 15
TI  - Indispensable role of endothelial nitric oxide synthase in caloric 
      restriction-induced cardioprotection against ischemia-reperfusion injury.
PG  - H894-903
LID - 10.1152/ajpheart.00333.2014 [doi]
AB  - Caloric restriction (CR) confers cardioprotection against ischemia-reperfusion 
      injury (IRI). We previously found that treatment with N(G)-nitro-l-arginine 
      methyl ester completely abrogates CR-induced cardioprotection and increases 
      nuclear sirtuin 1 (Sirt1) expression. However, it remains unclear whether 
      endothelial nitric oxide (NO) synthase (eNOS) plays a role in CR-induced 
      cardioprotection and Sirt1 activation. We subjected eNOS-deficient (eNOS(-/-)) 
      mice to either 3-mo ad libitum (AL) feeding or CR (-40%). Isolated perfused 
      hearts were subjected to 25-min global ischemia followed by 60-min reperfusion. 
      The degree of myocardial IRI in AL-fed eNOS(-/-) mice was more severe than that 
      in AL-fed wild-type mice. Furthermore, CR did not exert cardioprotection in 
      eNOS(-/-) mice. eNOS(-/-) mice exhibited elevated blood pressure and left 
      ventricular hypertrophy compared with wild-type mice, although they underwent CR. 
      Although nuclear Sir1 content was increased, the increases in cardiac Sirt1 
      activity with CR was absent in eNOS(-/-) mice. In eNOS(-/-) mice treated with 
      hydralazine, blood pressure and left ventricular weight became comparable with 
      CR-treated wild-type mice. However, CR-induced cardioprotection was not observed. 
      Resveratrol enhanced cardiac Sirt1 activity but failed to mimic CR-induced 
      cardioprotection in eNOS(-/-) mice. Finally, combination therapy with resveratrol 
      and hydralazine attenuated myocardial IRI and reduced infarct size in eNOS(-/-) 
      mice, and their effects were comparable with those observed in CR-treated 
      wild-type mice. These results demonstrate the essential roles of eNOS in the 
      development of CR-induced cardioprotection and Sirt1 activation during CR. The 
      combination of a relatively low dose of resveratrol with an adequate vasodilator 
      therapy might be useful for managing patients with endothelial dysfunction 
      associated with impaired NO bioavailability.
CI  - Copyright (c) 2015 the American Physiological Society.
FAU - Shinmura, Ken
AU  - Shinmura K
AD  - Department of Cardiology, Keio University School of Medicine, Tokyo, Japan; 
      shimmura@z5.keio.jp.
FAU - Tamaki, Kayoko
AU  - Tamaki K
AD  - Department of Cardiology, Keio University School of Medicine, Tokyo, Japan; Japan 
      Science and Technology Agency, Exploratory Research for Advanced Technology, 
      Suematsu Gas Biology Project, Tokyo, Japan; and.
FAU - Ito, Kentaro
AU  - Ito K
AD  - Department of Cardiology, Keio University School of Medicine, Tokyo, Japan;
FAU - Yan, Xiaoxiang
AU  - Yan X
AD  - Department of Cardiology, Keio University School of Medicine, Tokyo, Japan;
FAU - Yamamoto, Tsunehisa
AU  - Yamamoto T
AD  - Department of Cardiology, Keio University School of Medicine, Tokyo, Japan;
FAU - Katsumata, Yoshinori
AU  - Katsumata Y
AD  - Department of Cardiology, Keio University School of Medicine, Tokyo, Japan;
FAU - Matsuhashi, Tomohiro
AU  - Matsuhashi T
AD  - Department of Cardiology, Keio University School of Medicine, Tokyo, Japan;
FAU - Sano, Motoaki
AU  - Sano M
AD  - Department of Cardiology, Keio University School of Medicine, Tokyo, Japan;
FAU - Fukuda, Keiichi
AU  - Fukuda K
AD  - Department of Cardiology, Keio University School of Medicine, Tokyo, Japan;
FAU - Suematsu, Makoto
AU  - Suematsu M
AD  - Department of Biochemistry, Keio University School of Medicine, Tokyo, Japan; 
      Japan Science and Technology Agency, Exploratory Research for Advanced 
      Technology, Suematsu Gas Biology Project, Tokyo, Japan; and.
FAU - Ishii, Isao
AU  - Ishii I
AD  - Department of Biochemistry, Keio University School of Medicine, Tokyo, Japan; 
      Department of Biochemistry, Keio University Graduate School of Pharmaceutical 
      Sciences, Tokyo, Japan.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150213
PL  - United States
TA  - Am J Physiol Heart Circ Physiol
JT  - American journal of physiology. Heart and circulatory physiology
JID - 100901228
RN  - 0 (Stilbenes)
RN  - 0 (Vasodilator Agents)
RN  - 26NAK24LS8 (Hydralazine)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type III)
RN  - EC 3.5.1.- (Sirt1 protein, mouse)
RN  - EC 3.5.1.- (Sirtuin 1)
RN  - Q369O8926L (Resveratrol)
SB  - IM
MH  - Animals
MH  - *Caloric Restriction
MH  - Hydralazine/therapeutic use
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Myocardial Reperfusion Injury/diet therapy/drug therapy/*enzymology
MH  - Nitric Oxide Synthase Type III/genetics/*metabolism
MH  - Resveratrol
MH  - Sirtuin 1/metabolism
MH  - Stilbenes/therapeutic use
MH  - Vasodilator Agents/therapeutic use
OTO - NOTNLM
OT  - ischemia-reperfusion
OT  - myocardial infarction
OT  - nitric oxide synthase
OT  - resveratrol
OT  - sirtuin 1
EDAT- 2015/02/15 06:00
MHDA- 2016/01/01 06:00
CRDT- 2015/02/15 06:00
PHST- 2014/05/19 00:00 [received]
PHST- 2015/02/06 00:00 [accepted]
PHST- 2015/02/15 06:00 [entrez]
PHST- 2015/02/15 06:00 [pubmed]
PHST- 2016/01/01 06:00 [medline]
AID - ajpheart.00333.2014 [pii]
AID - 10.1152/ajpheart.00333.2014 [doi]
PST - ppublish
SO  - Am J Physiol Heart Circ Physiol. 2015 Apr 15;308(8):H894-903. doi: 
      10.1152/ajpheart.00333.2014. Epub 2015 Feb 13.