title: Reactive oxygen species partially mediate high dose angiotensin II-induced positive inotropic effect in cat ventricular myocytes.
abstract: BACKGROUND
  Reactive oxygen species, such as superoxide, are being increasingly recognized as key components of a vast array of signaling pathways. Angiotensin II is a well-recognized stimulus for superoxide production through NADPH oxidase activation and opening of the mitochondrial ATP-sensitive potassium channels (mKATP). A role for this mechanism has been proposed to explain several physiological effects of the peptide. The aim of this study was to evaluate the involvement of this mechanism in the inotropic response to 100nmol/L angiotensin II.
  
  
  METHODS
  Sarcomere shortening and intracellular pH (BCECF-epifluorescence technique) were evaluated in isolated cat ventricular myocytes placed in a perfusion chamber on the stage of an inverted microscope. Myocardial superoxide production was evaluated by the lucigenin quimioluminiscence method.
  
  
  RESULTS
  Angiotensin II (100nmol/L) increased~70% sarcomere shortening, effect that was only partially prevented by NADPH oxidase inhibition, mKATP channel blockade or inhibition of the cardiac Na(+)/H(+) exchanger (NHE-1). Moreover, angiotensin II stimulates NHE-1 activity by a NADPH oxidase-dependent mechanism. Myocardial superoxide production was also increased by angiotensin II, and this action was completely prevented either by NADPH oxidase inhibition or mKATP channel blockade.
  
  
  CONCLUSIONS
  The positive inotropic response to 100nmol/L angiotensin II is due to both ROS/NHE-1 dependent and independent pathways, this being a point of divergence with the signaling previously described to be triggered by lower concentrations of angiotensin II (i.e.: 1nmol/L).
authors: Centro de Investigaciones Cardiovasculares, Facultad de Ciencias Médicas, UNLP-CONICET, Argentina.
authors: Alejandra M
authors: AM
authors: Yeves
authors: Centro de Investigaciones Cardiovasculares, Facultad de Ciencias Médicas, UNLP-CONICET, Argentina.
authors: Claudia I
authors: CI
authors: Caldiz
authors: Centro de Investigaciones Cardiovasculares, Facultad de Ciencias Médicas, UNLP-CONICET, Argentina.
authors: Ernesto A
authors: EA
authors: Aiello
authors: Centro de Investigaciones Cardiovasculares, Facultad de Ciencias Médicas, UNLP-CONICET, Argentina.
authors: María C
authors: MC
authors: Villa-Abrille
authors: Centro de Investigaciones Cardiovasculares, Facultad de Ciencias Médicas, UNLP-CONICET, Argentina. Electronic address: iennis@med.unlp.edu.ar.
authors: Irene L
authors: IL
authors: Ennis
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D002316:Cardiotonic Agents / Q000494:pharmacology*; D002415:Cats; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006352:Heart Ventricles / Q000187:drug effects* / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D009200:Myocardial Contraction / Q000187:drug effects*; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors / Q000378:metabolism; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism; D012518:Sarcomeres / Q000187:drug effects / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D017923:Sodium-Hydrogen Exchangers / Q000037:antagonists & inhibitors / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism*
chemical_list: D002316:Cardiotonic Agents; D004791:Enzyme Inhibitors; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D017923:Sodium-Hydrogen Exchangers; C117780:mitochondrial K(ATP) channel; D013481:Superoxides; D000804:Angiotensin II; D019255:NADPH Oxidases
keywords: Angiotensin II; Inotropism; Isolated cardiomyocytes; NHE-1; Reactive oxygen species