title: Exercise protects against myocardial ischemia-reperfusion injury via stimulation of β(3)-adrenergic receptors and increased nitric oxide signaling: role of nitrite and nitrosothiols.
abstract: BACKGROUND
  Exercise training confers sustainable protection against ischemia-reperfusion injury in animal models and has been associated with improved survival following a heart attack in humans. It is still unclear how exercise protects the heart, but it is apparent that endothelial nitric oxide synthase (eNOS) and nitric oxide (NO) play a role.
  
  
  OBJECTIVE
  To determine the role of β(3)-adrenergic receptors (β(3)-ARs), eNOS activation, and NO metabolites (nitrite and nitrosothiols) in the sustained cardioprotective effects of exercise.
  
  
  RESULTS
  Here we show that voluntary exercise reduces myocardial injury in mice following a 4-week training period and that these protective effects can be sustained for at least 1 week following the cessation of the training. The sustained cardioprotective effects of exercise are mediated by alterations in the phosphorylation status of eNOS (increase in serine 1177 and decrease in threonine 495), leading to an increase in NO generation and storage of NO metabolites (nitrite and nitrosothiols) in the heart. Further evidence revealed that the alterations in eNOS phosphorylation status and NO generation were mediated by β(3)-AR stimulation and that in response to exercise a deficiency of β(3)-ARs leads to an exacerbation of myocardial infarction following ischemia-reperfusion injury.
  
  
  CONCLUSIONS
  Our findings clearly demonstrate that exercise protects the heart against myocardial ischemia-reperfusion injury by stimulation of β(3)-ARs and increased cardiac storage of nitric oxide metabolites (ie, nitrite and nitrosothiols).
authors.affiliation: Department of Surgery, Division of Cardiothoracic Surgery, Carlyle Fraser Heart Center, Emory University School of Medicine, Atlanta, GA 30308, USA.
authors.forename: John W
authors.initials: JW
authors.lastname: Calvert
authors.forename: Marah E
authors.initials: ME
authors.lastname: Condit
authors.forename: Juan Pablo
authors.initials: JP
authors.lastname: Aragón
authors.forename: Chad K
authors.initials: CK
authors.lastname: Nicholson
authors.forename: Bridgette F
authors.initials: BF
authors.lastname: Moody
authors.forename: Rebecca L
authors.initials: RL
authors.lastname: Hood
authors.forename: Amy L
authors.initials: AL
authors.lastname: Sindler
authors.forename: Susheel
authors.initials: S
authors.lastname: Gundewar
authors.forename: Douglas R
authors.initials: DR
authors.lastname: Seals
authors.forename: Lili A
authors.initials: LA
authors.lastname: Barouch
authors.forename: David J
authors.initials: DJ
authors.lastname: Lefer
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D004789:Enzyme Activation; D015444:Exercise; D006801:Humans; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D015428:Myocardial Reperfusion Injury / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control*; D009569:Nitric Oxide / Q000235:genetics / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III / Q000235:genetics / Q000378:metabolism; D009573:Nitrites / Q000378:metabolism*; D009603:Nitroso Compounds / Q000378:metabolism*; D010805:Physical Conditioning, Animal; D022702:Receptors, Adrenergic, beta-3 / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors
chemical_list: D009573:Nitrites; D009603:Nitroso Compounds; D022702:Receptors, Adrenergic, beta-3; D009569:Nitric Oxide; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III; C496315:Nos3 protein, mouse