title: Enhanced cardiac preconditioning in the isolated heart of the transgenic ((mREN-2) 27) hypertensive rat.
abstract: OBJECTIVE
  Cardiac preconditioning represents an important cardioprotective mechanism which limits myocardial ischaemic damage. The aim of this investigation was to assess the impact of preconditioning in hypertension, which is a major risk factor for ischaemic heart disease.
  
  
  METHODS
  Hearts isolated from male transgenic ((mREN-2)27) hypertensive (TGH) rats, and their normotensive controls (Hannover Sprague-Dawley; SD rats), were perfused at constant flow using the Langendorff technique, and were subjected to either ischaemic preconditioning (3 x 4 min ischaemia) or continuous perfusion. Global ischaemia was then induced for 30 min, followed by 60 min of reperfusion, during which time mechanical performance was assessed (left ventricular developed pressure (LVDP), heart rate, and end-diastolic pressure).
  
  
  RESULTS
  In the absence of preconditioning, mechanical performance was substantially depressed on reperfusion, and there was no difference between TGH hearts and SD hearts (area under the curve (AUC) for the LVDP (LVDP0-60) plot against time for reperfusion = 356 +/- 115 and 296 +/- 206 mmHg.min, respectively). Cardiac preconditioning caused significant protection in both groups, but this was significantly (P < 0.05) greater (3-fold) in the TGH hearts (AUC for LVDP0-60 = 3349 +/- 610 mmHg.min) compared to the SD hearts (AUC for LVDP0-60 = 1153 +/- 527 mmHg.min). In both groups, preconditioning induced significant protection of diastolic function. The enhanced effects of preconditioning on mechanical performance in the TGH hearts were unaffected by the angiotensin AT1-receptor antagonist, losartan (3 microM). However, losartan did partially reverse the beneficial effects of preconditioning on post-ischaemic diastolic function in the TGH hearts.
  
  
  CONCLUSIONS
  The results of the present investigation clearly show that cardiac preconditioning is substantially enhanced in hearts from TGH rats. Furthermore, the beneficial effects of preconditioning on diastolic function, but not mechanical performance, in TGH hearts is partially mediated by AT1-receptors.
authors.affiliation: Department of Physiology and Pharmacology, University of Nottingham Medical School, Queen's Medical Centre, UK. michael.randall@nottingham.ac.uk
authors.forename: M D
authors.initials: MD
authors.lastname: Randall
authors.forename: S M
authors.initials: SM
authors.lastname: Gardiner
authors.forename: T
authors.initials: T
authors.lastname: Bennett
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D000959:Antihypertensive Agents / Q000494:pharmacology; D001713:Biphenyl Compounds / Q000494:pharmacology; D006973:Hypertension / Q000503:physiopathology*; D007093:Imidazoles / Q000494:pharmacology; D019157:Ischemic Preconditioning, Myocardial; D019808:Losartan; D008297:Male; D017202:Myocardial Ischemia / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012084:Renin-Angiotensin System / Q000502:physiology; D013777:Tetrazoles / Q000494:pharmacology
chemical_list: D000959:Antihypertensive Agents; D001713:Biphenyl Compounds; D007093:Imidazoles; D013777:Tetrazoles; D019808:Losartan