title: Various inotropic effects of angiotensin II in post-ischaemic rat hearts depending on ischaemic time with possible involvement of protein kinase C.
abstract: OBJECTIVE
  The present study investigated if the inotropic effect of angiotensin II (AngII) is altered during post-ischaemic reperfusion in hearts subjected to mild and severe ischaemia. The possible involvement of protein kinase C (PKC) in the change in the inotropic effect was also investigated.
  
  
  METHODS
  Isolated Langendorff-perfused rat hearts were perfused under constant flow with oxygenated Krebs-Henseleit buffer and paced at 360 beats min(-1). A saline-filled balloon catheter inserted into the left ventricle was used for measurement of contractile force. In the first series of experiments, hearts were subjected to continuous perfusion, 15- or 25-min global ischaemia followed by 45-min reperfusion. At the end of reperfusion, 0.1 micromol L(-1) AngII was infused for 5 min. In a second series of experiments, AngII was infused in hearts subjected to 25-min ischaemia followed by 45-min reperfusion in the absence or presence of the PKC inhibitor chelerythrine chloride (5 micromol L(-1)).
  
  
  RESULTS
  The current study demonstrates that AngII exerts a positive inotropic effect in normoxic hearts with an increase of left ventricular developed pressure (LVDP) by 11% (P<0.05 vs. prior to AngII infusion). In post-ischaemic hearts subjected to 15-min ischaemia no effect of AngII was observed. In hearts subjected to 25 min of ischaemia, however, AngII evoked a negative inotropic response with a decrease of LVDP by 18% (P<0.05 vs. prior to AngII infusion). The negative inotropic effect of AngII was inhibited by the PKC inhibitor chelerythrine chloride.
  
  
  CONCLUSIONS
  AngII exerts negative inotropic effect in severely injured post-ischaemic heart, possibly through the PKC pathway.
authors.affiliation: Department of Integrative Pharmacology, Astrazeneca R & D Mölndal, Mölndal, Sweden.
authors.forename: Q-D
authors.initials: QD
authors.lastname: Wang
authors.forename: E
authors.initials: E
authors.lastname: Nygren
mesh_terms: D000470:Alkaloids; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D053119:Benzophenanthridines; D001794:Blood Pressure / Q000187:drug effects; D002316:Cardiotonic Agents / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D017202:Myocardial Ischemia / Q000378:metabolism / Q000503:physiopathology*; D015425:Myocardial Reperfusion / Q000379:methods; D009206:Myocardium / Q000378:metabolism; D010617:Phenanthridines / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000470:Alkaloids; D053119:Benzophenanthridines; D002316:Cardiotonic Agents; D010617:Phenanthridines; D000804:Angiotensin II; C016299:chelerythrine; D011493:Protein Kinase C