Enhanced cardiac preconditioning in the isolated heart of the transgenic ž ž / / mREN - 2 27 hypertensive rat

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 ŽŽ . . Ž . disease. Methods: Hearts isolated from male transgenic mREN-2 27 hypertensive TGH rats, and their normotensive controls Ž . Hannover Sprague-Dawley; SD rats , were perfused at constant flow using the Langendorff technique, and were subjected to either Ž . ischaemic preconditioning 3=4 min ischaemia or continuous perfusion. Global ischaemia was then induced for 30 min, followed by 60 Ž Ž . 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, Ž Ž . Ž . and there was no difference between TGH hearts and SD hearts area under the curve AUC for the LVDP LVDP plot against time 0 – 60 . for reperfusion s 356"115 and 296"206 mmHgPmin, respectively . Cardiac preconditioning caused significant protection in both Ž . Ž . Ž . groups, but this was significantly P-0.05 greater 3-fold in the TGH hearts AUC for LVDP s 3349"610 mmHgPmin 0 – 60 Ž . compared to the SD hearts AUC for LVDP s 1153"527 mmHgPmin . In both groups, preconditioning induced significant 0 – 60 protection of diastolic function. The enhanced effects of preconditioning on mechanical performance in the TGH hearts were unaffected Ž . by the angiotensin AT -receptor antagonist, losartan 3 mM . However, losartan did partially reverse the beneficial effects of 1 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 AT -receptors. 1