ANG II-related myocardial damage:: role of cardiac sympathetic catecholamines and β-receptor regulation

The objectives of this study were I) to determine whether ANG II-induced myocardial damage (ANG Dam) is mediated via the beta(1)-adrenergic receptor, 2) to elucidate whether adrenal medulla or cardiac sympathetic neuron catecholamines are responsible for ANG Dam, and 3) to determine whether the lack of damage after 3 days of elevated ANG II levels is due to beta(1)-receptor downregulation. To this end, ANG II was administered to rats I) that were treated with a beta-receptor blocker 2) after adrenal medullectomy and/or cardiac sympathetomy,: and 3) for 3 or 8 days. ANG II caused both myocyte necrosis and coronary vascular damage after adrenal medullectomy but not after cardiac sympathectomy. There was a 38 and 55% decrease in beta-receptor density after 3 and 8 days, respectively, of ANG II infusion, and an upregulation to control levels 5 days after a 3-day ANG II infusion was stopped. We conclude that cardiac sympathetic neuron catecholamines are responsible for ANG Dam and that the acute nature of this damage is associated with a downregulation of beta 1-adrenergic receptors.