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

• Published in: American journal of physiology. Heart and circulatory physiology 1998-08, Vol.275 (2), p.H534-H541
• Main Authors: Henegar, Jeffrey R, Schwartz, Dean D, Janicki, Joseph S
• Format: Article
• Language: English
• ISSN: 0363-6135; 1522-1539
• DOI: 10.1152/ajpheart.1998.275.2.H534

Department of Physiology and Pharmacology, Auburn University, Auburn, Alabama 36849 The objectives of this study were 1 ) to determine whether ANG II-induced myocardial damage (ANG Dam) is mediated via the 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 1 -receptor downregulation. To this end, ANG II was administered to rats 1 ) that were treated with a -receptor blocker, 2 ) after adrenal medullectomy and/or cardiac sympathectomy, 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 -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 1 -adrenergic receptors. myocyte necrosis; atenolol; adrenal medullectomy; cardiac sympathectomy; coronary arteriolar damage