title: [Role of reactive oxygen species, nitric oxide and mitochondrial K(ATP) channels in TNF-alpha induced cardioprotection].
abstract: OBJECTIVE
  To explore the cardiac effect of TNF-alpha in postischemic heart and the possible mechanism.
  
  
  METHODS
  Langendorff perfused rat heart was used to evaluate the contractile properties of myocardium by intraventricular pressure measurement. The isolated rat heart underwent 20 min of global ischemia followed by 20 min of reperfusion. The level of lactate dehydrogenase (LDH) in the coronary effluent was measured to evaluate the cardiac injury. And the activity of manganese superoxide dismutase (Mn-SOD) in myocardium was measured.
  
  
  RESULTS
  Perfusion with TNF-alpha (104 U/L) attenuated the inhibitory effects induced by ischemia/reperfusion on left ventricular developed pressure (LVDP), left ventricular end-diastolic pressure(LVEDP), maximal rise/fall rate of left ventricular pressure (+/- dP/dtmax) and rate pressure product (LVDP multiplied by heart rate, LVDP x HR). TNF-alpha significantly decreased the release of LDH (P < 0.05) and increased the activity of Mn-SOD in the myocardium (P < 0.05). Antioxidant 2-MPG (0.3 mmol/L), NOS inhibitor L-NAME (0.5 mmol/L) or mitochondrial selective KATP channel inhibitor 5-HD (100 micromol/L) attenuated the increase in LVDP, +/- dP/dtmax and LVDP x HR, and decrease in LVEDP induced by TNF-alpha in ischemia/reperfusion heart, respectively. And the effects of TNF-alpha in reducing the levels of LDH and increasing the Mn-SOD activity were also attenuated by 2-MPG, L-NAME or 5-HD, respectively.
  
  
  CONCLUSIONS
  TNF-alpha pretreatment attenuates the myocardial injury induced by ischemia/reperfusion, which coincides with the increasing of myocardial Mn-SOD activity. Reactive oxygen species, nitric oxide and mitochondrial KATP channels are involved in the cardioprotection induced by TNF-alpha.
authors.affiliation: Department of Physiology, Zhejiang University School of Medicine, Hangzhou 310031, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Fu
authors.forename: Qiang
authors.initials: Q
authors.lastname: Xia
authors.forename: Chun-mei
authors.initials: CM
authors.lastname: Cao
authors.forename: Qin
authors.initials: Q
authors.lastname: Gao
authors.forename: Hui
authors.initials: H
authors.lastname: Yao
authors.forename: Hong-feng
authors.initials: HF
authors.lastname: Jin
mesh_terms: D000818:Animals; D002316:Cardiotonic Agents / Q000627:therapeutic use; D006321:Heart / Q000187:drug effects; D066298:In Vitro Techniques; D019157:Ischemic Preconditioning, Myocardial / Q000379:methods*; D008297:Male; D008929:Mitochondria, Heart / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D015221:Potassium Channels / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000627:therapeutic use*
chemical_list: D002316:Cardiotonic Agents; D015221:Potassium Channels; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; C117780:mitochondrial K(ATP) channel; D009569:Nitric Oxide