title: Angiotensin II (AII)-induced myocyte necrosis: role of the AII receptor.
abstract: Pathophysiologic levels of angiotensin II (AII) produce myocyte necrosis. We investigated whether the cardiotoxic effects of AII are mediated through the AII type I receptor (AT1). Seven groups (4-6 rats/group) were given AII (150 ng/min) alone or in combination with the AT1 antagonist losartan (7.5 mg/day). Groups were as follows: A1, A4, and L1 received AII for 2 days; A2 and L2 received AII for 9 days; and A3 and L3 received AII for 2 days and again for 2 days 5 days later. Groups L1, L2, and L3 also received losartan 2 days before and throughout the AII infusion period. All rats except those in group A4 were killed at the end of their respective infusion periods (group A4 rats were killed 7 days after infusion). Group A1 had multifocal areas of recent myocyte injury. Groups A2 and A4 had multifocal scars and only a few new areas of myocyte damage. Group A3, in addition to scar formation, had de novo areas of necrosis. There was no evidence of myocyte necrosis in groups L1, L2, and L3. Thus, AII-related myocyte necrosis is receptor mediated. Moreover, a chronic increase in AII appears to cause cardioprotective downregulation of the AT1 receptor.
authors.affiliation: Department of Internal Medicine, University of Missouri, Columbia 65212.
authors.forename: A
authors.initials: A
authors.lastname: Kabour
authors.forename: J R
authors.initials: JR
authors.lastname: Henegar
authors.forename: J S
authors.initials: JS
authors.lastname: Janicki
mesh_terms: D000804:Angiotensin II / Q000633:toxicity*; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology; D006321:Heart / Q000187:drug effects*; D007093:Imidazoles / Q000494:pharmacology; D019808:Losartan; D008297:Male; D009206:Myocardium / Q000473:pathology; D009336:Necrosis; D051381:Rats; D017207:Rats, Sprague-Dawley; D011945:Receptors, Angiotensin / Q000502:physiology*; D013777:Tetrazoles / Q000494:pharmacology
chemical_list: D057911:Angiotensin Receptor Antagonists; D001713:Biphenyl Compounds; D007093:Imidazoles; D011945:Receptors, Angiotensin; D013777:Tetrazoles; D000804:Angiotensin II; D019808:Losartan