ANG II-induced cardiac molecular and cellular events: Role of aldosterone

Wenyuan Zhao, Robert A. Ahokas, Karl Weber, Yao Sun

Research output: Contribution to journalArticle

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Abstract

Chronic elevation of circulating ANG II is associated with cardiac remodeling in patients with hypertension and heart failure. The underlying mechanisms, however, are not completely defined. Herein, we studied ANG II-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 ANG II-induced cardiac remodeling. In ANG II-treated rats, and compared with controls, we found: 1) the expression of proinflammatory/ profibrogenic mediators was significantly increased in the perivascular space and at the sites of microscopic injury in both ventricles; 2) macrophages and myofibroblasts were primary repairing cells at these sites, together with increased fibrillar collagen volume; 3) apoptotic macrophages and myofibroblasts were evident at the same sites; 4) NADPH oxidase (gp91phox) was significantly enhanced at these regions and primarily expressed by macrophages, whereas superoxide dismutase and catalase levels remained unchanged; 5) plasma 8-isoprostane levels were significantly increased; and 6) blood pressure was significantly elevated. Losartan treatment completely prevented cardiac oxidative stress as well as molecular/cellular responses and normalized blood pressure. Spironolactone treatment partially suppressed the cardiac inflammatory/fibrogenic responses and redox state. Thus chronic elevation of circulating ANG II is accompanied by a proinflammatory/profibrogenic phenotype involving vascular and myocardial remodeling in both ventricles. Enhanced reactive oxygen species production at these sites and increased plasma 8-isoprostane indicate the involvement of oxidative stress in ANG II-induced cardiac injury. ALDO contributes, in part, to ANG II-induced cardiac molecular and cellular responses.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume291
Issue number1
DOIs
StatePublished - Jul 12 2006

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8-epi-prostaglandin F2alpha
Aldosterone
Myofibroblasts
Macrophages
Oxidation-Reduction
Oxidative Stress
Fibrillar Collagens
Blood Pressure
Spironolactone
Losartan
NADPH Oxidase
Wounds and Injuries
Catalase
Superoxide Dismutase
Reactive Oxygen Species
Heart Failure
Hypertension
Phenotype
Therapeutics

All Science Journal Classification (ASJC) codes

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

ANG II-induced cardiac molecular and cellular events : Role of aldosterone. / Zhao, Wenyuan; Ahokas, Robert A.; Weber, Karl; Sun, Yao.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 291, No. 1, 12.07.2006.

Research output: Contribution to journalArticle

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