Md. Randall et al., ENHANCED CARDIAC PRECONDITIONING IN THE ISOLATED HEART OF THE TRANSGENIC ((MREN-2)27) HYPERTENSIVE RAT, Cardiovascular Research, 33(2), 1997, pp. 400-409
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.