title: The role of nitric oxide in endotoxin-induced cardiodepression.
abstract: OBJECTIVE
  To determine the participation of inducible nitric oxide synthase (iNOS) in cardiodepressive phenomena during late preconditioning caused by subtoxic doses of lipopolysaccharide (LPS).
  
  
  METHODS
  Spontaneously beating hearts isolated from male Wistar rats (350 g to 400 g), intact or preconditioned with LPS (0.25 mg/kg given intraperitoneally 18 h before heart excision), were used to measure contractile performance during 30 min of ischemia and 40 min of reperfusion in the Langendorff mode. For selective iNOS blockade, hearts were perfused with phenylene-1,3-bis(ethane-2-isothiourea) (50 nmol/L). Expression of iNOS (determined using Western blotting) and NOS activities were determined in frozen myocardial tissues.
  
  
  RESULTS
  Subtoxic doses of LPS caused iNOS induction in the heart and depression of contractile function, but improved heart postischemic recovery. In all groups of animals, expression of iNOS was higher in the right than left ventricles. Ischemia and postischemic reperfusion of intact heart intensified production of nitric oxide (NO), predominantly by iNOS. The preconditioning led to iNOS activation during ischemia in the left ventricle and iNOS depression in the right ventricle, owing to feedback caused by the initially higher iNOS expression and activity in the right ventricle. Postischemic reperfusion diminished NOS activities in preconditioned myocardial tissues. Blockade of iNOS significantly slowed preconditioned heart recovery and partially restored left ventricular developed pressure, but only after 20 min of reperfusion.
  
  
  CONCLUSIONS
  iNOS-produced NO plays a role in the development of delayed cardioprotection and cardiodepressive effects (in part) after extravasal administration of a minimal dose of endotoxin.
authors.affiliation: Bogomoletz Institute of Physiology, National Academy of Sciences of Ukraine;
authors.forename: Alla G
authors.initials: AG
authors.lastname: Portnychenko
authors.forename: Olga Yu
authors.initials: OY
authors.lastname: Harmatina
authors.forename: Anatolij V
authors.initials: AV
authors.lastname: Kotsuruba
authors.forename: Oleksij O
authors.initials: OO
authors.lastname: Moybenko