ENHANCED CARDIAC PRECONDITIONING IN THE ISOLATED HEART OF THE TRANSGENIC ((MREN-2)27) HYPERTENSIVE RAT

Ohjective: Cardiac preconditioning represents an important cardioprote ctive mechanism which limits myocardial ischaemic damage. The aim of t his investigation was to assess the impact of preconditioning in hyper tension, which is a major risk factor for ischaemic heart disease. Met hods: Hearts isolated from male transgenic ((mREN-2)27) hypertensive ( TGH) rats, and their normotensive controls (Hannover Sprague-Dawley; S D rats), were perfused at constant flow using the Langendorff techniqu e, and were subjected to either ischaemic preconditioning (3 x 4 min i schaemia) or continuous perfusion. Global ischaemia was then induced f or 30 min, followed by 60 min of reperfusion, during which time mechan ical performance was assessed (left ventricular developed pressure (LV DP), 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 (AUG) for the LVDP (LVDP(0-60)) plot aga inst time for reperfusion = 356 +/- 115 and 296 +/- 206 mmHg . min, re spectively). Cardiac preconditioning caused significant protection in both groups, but this was significantly (P < 0.05) greater (3-fold) in the TGH hearts (AUC for LVDP(0-60) = 3349 +/- 610 mmHg . min) compare d to the SD hearts (AUG for LVDP(0-60) = 1153 +/- 527 mmHg . min). In both groups, preconditioning induced significant protection of diastol ic function. The enhanced effects of preconditioning on mechanical per formance in the TGH hearts were unaffected by the angiotensin AT(1)-re ceptor antagonist, losartan (3 mu M). However, losartan did partially reverse the beneficial effects of preconditioning on post-ischaemic di astolic function in the TGH hearts. Conclusions: The results of the pr esent investigation clearly show that cardiac preconditioning is subst antially 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 AT(1)-receptors.