Heart failure: how important is cellular sequestration? - The role of the renin-angiotensin-aldosterone system

Heart failure, which is classically described as a pathologic process characterized by a decline of heart contractility, involves a complex set of alterations like the release of inflammatory cytokines, endothelin, angiotensin II and aldosterone. These abnormalities cause appreciable changes at cellular and molecular levels with consequent impairment of cell coupling, impulse propagation as well as morphologic alterations. In the present review the question whether cellular sequestration elicited by impairment of cell coupling and interstitial fibrosis plays a role on the development of the disease is discussed and the role of the plasma and cardiac renin-angiotensin-aldosterone systems on the process of cellular sequestration is described. The possible role of an intracellular renin-angiotensin system on intercellular signaling is also discussed. The beneficial role of the angiotensin-converfing enzyme inhibitors is related to the improvement of cellular synchronization which seems related to different factors like increment of cell coupling, hyperpolarization of cell membrane and morphologic remodeling including a decrease of interstitial fibrosis and ventricular hypertrophy. (C) 2004 Elsevier Ltd. All rights reserved.