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ANGIOTENSIN II‐INDUCED CARDIAC MOLECULAR AND CELLULAR EVENTS: ROLE OF ALDOSTERONE
Author(s) -
Zhao Dan,
Yan Ran,
Zhao Wenyuan,
Sun Yao
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.a1178-b
Subject(s) - angiotensin ii , medicine , endocrinology , cardiac fibrosis , losartan , aldosterone , heart failure , proinflammatory cytokine , oxidative stress , chemistry , renin–angiotensin system , blood pressure , inflammation
Chronic elevation of circulating angiotensin (Ang)II is associated to cardiac remodeling in patients with hypertension and chronic heart failure. The underlying mechanisms, however, are not completely defined. Herein, we studied AngII induced molecular and cellular events in the rat heart as well as their links to the redox state. We also addressed the potential contribution of aldosterone (ALDO) on AngII induced cardiac damage. SD rats were treated with AngII (150ug/min) for 4 wks. At sites of perivascular space and microscopic injury in AngII treated rats, we found: 1) ICAM‐1, MCP‐1, TGF‐β1, type I collagen, mRNAs were significantly increased; 2) macrophages and myofibroblasts (myoFb) were primary repairing cells, together with increased collagen volume; 3) apoptotic myocytes, macrophages and myoFb were evident; and 4) the expression of gp91 phox was significantly enhanced, while SOD and catalase mRNA and protein levels remained unchanged. Plasma 8‐isoprostane levels and blood pressure were significantly elevated in AngII treated rats. Losartan treatment completely prevented above cardiac molecular and cellular responses and normalized blood pressure. Spironolactone treatment suppressed the cardiac inflammatory/fibrogenic responses as well as redox state. Thus, chronic elevation of circulating AngII is accompanied by a proinflammatory/profibrogenic phenotype involving vascular and myocardial remodeling. Oxidative stress is involved in AngII induced cardiac injury. ALDO, in part, mediates AngII‐induced cardiac molecular and cellular responses.