Catecholamine response to chronic ANG II infusion and its role in myocyte and coronary vascular damage.
Acute elevations in circulating angiotensin II (ANG II) are known to increase circulating norepinephrine (NE) levels. However, the time course of catecholamine release relative to chronic ANG II infusion is not known. Furthermore, it is unknown if this ANG II-induced catecholamine release is ANG II type 1 (AT1) receptor mediated or whether the increase in serum catecholamines is responsible for the myocyte and coronary vascular damage seen within the first 3 days of chronic ANG II infusion. Therefore, we examined the influence of chronic ANG II stimulation on serum catecholamine levels with and without AT1 blockade and the effect of beta-blockade on ANG II-induced myocyte and coronary vascular damage. The results indicate that NE release is AT1 mediated, but NE is not significantly elevated until day 4 of ANG II infusion after which it remains elevated. beta-Blockade prevented most ANG II-related myocyte necrosis and coronary vascular damage. Therefore, myocyte and coronary vascular damage do not appear to be related to increased serum NE levels, but instead may be due to the release of neural catecholamines within the heart.
Henegar
J R
JR
Department of Internal Medicine, University of Missouri, Columbia 65212, USA.
Brower
G L
GL
Kabour
A
A
Janicki
J S
JS
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000804:Angiotensin II / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D003331:Coronary Vessels / Q000187:drug effects* / Q000473:pathology*; D006321:Heart / Q000187:drug effects*; D007262:Infusions, Intravenous; D008297:Male; D009206:Myocardium / Q000473:pathology*; D009336:Necrosis; D009638:Norepinephrine / Q000097:blood*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011945:Receptors, Angiotensin / Q000502:physiology; D013997:Time Factors
D000319:Adrenergic beta-Antagonists; D057911:Angiotensin Receptor Antagonists; D011945:Receptors, Angiotensin; D000804:Angiotensin II; D009638:Norepinephrine