ANGIOTENSIN-II (AII)-INDUCED MYOCYTE NECROSIS - ROLE OF THE AII-RECEPTOR

Pathophysiologic levels of angiotensin II (AII) produce myocyte necros is. We investigated whether the cardiotoxic effects of AII are mediate d through the AII type 1 receptor (AT1). Seven groups (4-6 rats/group) were given AII (150 ng/min) alone or in combination with the AT1 anta gonist losartan (7.5 mg/day). Groups were as follows: Al, A4, and L1 r eceived 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 L 1, L2, and L3 also received losartan 2 days before and throughout the AII infusion period. AII rats except those in group A4 were killed at the end of their respective infusion periods (group A4 rats were kille d 7 days after infusion). Group A1 had multifocal areas of recent myoc yte injury. Groups A2 and A4 had multifocal scars and only a few new a reas of myocyte damage. Group A3, in addition to scar formation, had d e 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 cardio protective downregulation of the AT1 re ceptor.