ANG II-related myocardial damage: role of cardiac sympathetic catecholamines and beta-receptor regulation.
The objectives of this study were 1) to determine whether ANG II-induced myocardial damage (ANG Dam) is mediated via the beta1-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 beta1-receptor downregulation. To this end, ANG II was administered to rats 1) that were treated with a beta-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 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 beta1-adrenergic receptors.
Department of Physiology and Pharmacology, Auburn University, Auburn, Alabama 36849, USA.
J R
JR
Henegar
D D
DD
Schwartz
J S
JS
Janicki
D000313:Adrenal Medulla / Q000502:physiology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000804:Angiotensin II / Q000097:blood* / Q000633:toxicity*; D000818:Animals; D001262:Atenolol / Q000494:pharmacology*; D002395:Catecholamines / Q000378:metabolism; D015536:Down-Regulation; D006321:Heart / Q000187:drug effects / Q000294:innervation / Q000502:physiology*; D007262:Infusions, Intravenous; D008297:Male; D009206:Myocardium / Q000378:metabolism / Q000473:pathology*; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018342:Receptors, Adrenergic, beta-1 / Q000096:biosynthesis*; D013562:Sympathectomy; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000502:physiology*; D013997:Time Factors
D000319:Adrenergic beta-Antagonists; D002395:Catecholamines; D018342:Receptors, Adrenergic, beta-1; D000804:Angiotensin II; D001262:Atenolol