Angiotensin II: a double-edged sword in inflammation

Abstract

Clinical and basic research has increased our knowledge of the actions of the vasoactive hormone angiotensin II (Ang II), showing that it has multifunctional properties beyond its hemodynamic effects. It is commonly accepted that Ang II is a growth factor that participates in pathological settings, including renal diseases. However, a new aspect of this peptide is coming into focus: its potential role as a proinflammatory modulator. In this review, we summarize the apparently confusing information about the properties of Ang II and discuss its relations to the inflammatory process, as well as the potential mechanisms mediated by activation of nuclear transcription factors. Ang II seems to participate in the key events of the inflammatory response: First, it increases vascular permeability (via prostaglandins and vascular endothelial cell growth factor/vascular permeability factor) thus initiating the inflammatory process. Second, it participates in the recruitment of infiltrating cells into the tissues through direct activation of the inflammatory cells or by regulation of the expression of adhesion molecules and chemokines by resident cells. Finally, Ang II may contribute to tissue repair by regulation of cell growth and matrix synthesis. The renin-angiotensin system (RAS) thus appears to serve as a vascular inflammatory regulator and may even participate in immunologically-induced inflammation. However, more often activation of the RAS has an undesirable outcome, such as overhealing, because the inflammatory repair response itself involves a functionally imperfect system.