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 that this hypertrophy may also depend, at least partially, on the increase of local production of angiotensin II secondary to the activation of the cardiac renin-angiotensin system. In this study we investigated the effects of isoproterenol on the activity of angiotensin-converting enzyme (ACE) in the heart and also in the aorta and plasma. Male Wistar rats weighing 250 to 305 g were treated with a dose of (+/-)-isoproterenol (0.3 mg kg-1 day-1, N = 8) sufficient to produce cardiac hypertrophy without deleterious effects 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 activity was determined in vitro in the four cardiac chambers, aorta and plasma by a fluorimetric assay. A significant hypertrophy was observed in both ventricular chambers. ACE activity in the atria remained constant after isoproterenol 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 isoproterenol (41 +/- 3 to 27 +/- 2 nmol His-Leu g-1 min-1) while it remained unchanged in the plasma. These data suggest that ACE expression in the heart can be increased by stimulation of beta-adrenoceptors. However, this effect is not observed on other local renin-angiotensin systems, such as 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.
Busatto
V C
VC
Departamento de Biologia, Universidade Federal do Espírito Santo, Vitória, Brasil.
Cunha
V
V
Cicilini
M A
MA
Mill
J G
JG
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000804:Angiotensin II / Q000378:metabolism; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000378:metabolism; D000818:Animals; D001011:Aorta / Q000187:drug effects* / Q000201:enzymology*; D006325:Heart Atria / Q000187:drug effects; D006352:Heart Ventricles / Q000187:drug effects; D007545:Isoproterenol / Q000494:pharmacology*; D008297:Male; D009206:Myocardium / Q000201:enzymology*; D010949:Plasma / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D012084:Renin-Angiotensin System / Q000187:drug effects* / Q000502:physiology*
D000318:Adrenergic beta-Agonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D000804:Angiotensin II; D007545:Isoproterenol