Angiotensin II receptor blockade attenuates the deleterious effects of exercise training on post-MI ventricular remodelling in rats

Jain, Mohit; Liao, Ronglih; Ngoy, Soeun; Whittaker, Peter; Apstein, Carl S.; Eberli, Franz R. (2000). Angiotensin II receptor blockade attenuates the deleterious effects of exercise training on post-MI ventricular remodelling in rats. Cardiovascular research, 46(1), pp. 66-72. Elsevier Science 10.1016/S0008-6363(99)00429-0

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Objectives: The effects of exercise training on LV remodelling following large anterior myocardial infarction (MI) remains controversial. Blockade of the renin–angiotensin system has been shown to prevent ventricular dilation and deleterious remodeling. We therefore tested, in a rat model of chronic MI, whether any potentially deleterious effects of exercise on post-MI remodelling could be ameliorated by angiotensin II receptor blockade. Methods: Male Wistar rats underwent coronary ligation or sham operation. Treatment with losartan (10 mg/kg/day) began 1 week post-MI and moderate treadmill exercise (25 m/min, 60 min/day, 5 days/week) was initiated 2 weeks post-MI. Systolic and diastolic pressure–volume relationships were measured in isolated, red-cell perfused, isovolumically beating hearts 8 weeks post-MI. Morphometric measurements were performed in trichrome stained cross sections of the heart. Five groups of animals were compared: sham (n=13), control MI (MI; n=11), MI plus losartan (MI–Los; n=13), MI plus exercise (MI–Ex; n=10) and MI plus exercise and losartan (MI–Ex–Los; n=12). Results: Infarct size (% of left ventricle, LV) was similar among the infarcted groups [MI=43±4%, MI–Los=49±2%, MI–Ex=45±1%, MI–Ex–Los=48±2% (NS)]. Exercise, losartan and exercise+losartan treatments all attenuated LV dilation post-MI to a similar degree. Exercise training increased LV developed pressure in both untreated and losartan treated hearts (P<0.05 vs. other MI groups). In addition, exercise resulted in additional scar thinning in untreated hearts, while no additional scar thinning was seen in post-infarct hearts receiving both losartan and exercise. Conclusions: Following large anterior MI, losartan attenuated LV dilation and scar thinning. In untreated animals, exercise decreased dilation, but also contributed to scar thinning. Therefore, exercise concurrent with blockade of the renin–angiotensin system may provide optimal therapeutic benefit following large anterior MI.

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