Differential effects of isoproterenol on the activity of angiotensin-converting enzyme in the rat heart and aorta

The excessive stimulation of beta-adrenergic receptors in the heart induces myocardial hypertrophy. There are several experimental data suggesting tha t this hypertrophy may also depend, at least partially, on the increase of local production of angiotensin II secondary to the activation of the cardi ac renin-angiotensin system. In this study we investigated the effects of i soproterenol on the activity of angiotensin-converting enzyme (ACE) in the heart and also in the aorta and plasma. Male Wistar rats weighing 250 to 30 5 g were treated with a dose of (+/-)-isoproterenol (0.3 mg kg(-1) day(-1), N = 8) sufficient to produce cardiac hypertrophy without deleterious effec ts on the pumping capacity of the heart. Control rats (N = 7) were treated with vehicle (corn oil). The animals were killed one week later. ACE activi ty was determined in vitro in the four cardiac chambers, aorta and plasma b y a fluorimetric assay. A significant hypertrophy was observed in both vent ricular chambers. ACE activity in the atria remained constant after isoprot erenol treatment. There was a significant increase (P<0.05) of ACE activity in the right ventricle (6.9 +/- 0.9 to 8.2 +/- 0.6 nmol His-Leu g(-1) min( -1)) and in the left ventricle (6.4 +/- 1.1 to 8.9 +/- 0.8 nmol His-Leu g(- 1) min(-1)). In the aorta, however, ACE activity decreased (P<0.01) after i soproterenol (41 +/- 3 to 27 +/- 2 nmol His-Leu g(-1) min(-1)) while it rem ained unchanged;. in the plasma. These data suggest that ACE expression in the heart can be increased by stimulation of beta-adrenoceptors. However, t his effect is not observed on other local renin-angiotensin systems, such a s the aorta. Our data also suggest that the increased sympathetic discharge and the elevated plasma concentration of catecholamines may contribute to the upregulation of ACE expression in the heart after myocardial infarction and heart failure.