Review
Inflammation and angiotensin II

https://doi.org/10.1016/S1357-2725(02)00271-6Get rights and content

Abstract

Angiotensin II (AngII), the major effector peptide of renin–angiotensin system (RAS), is now recognized as a growth factor that regulates cell growth and fibrosis, besides being a physiological mediator restoring circulatory integrity. In the last few years, a large number of experimental studies has further demonstrated that AngII is involved in key events of the inflammatory process. Here, we summarize the wide variety of AngII functions and discuss them in relation with the inflammatory cascade. AngII increases vascular permeability (via the release of prostaglandins and vascular endothelial cell growth factor or rearrangement of cytoskeletal proteins) that initiates the inflammatory process. AngII could contribute to the recruitment of inflammatory cells into the tissue through the regulation of adhesion molecules and chemokines by resident cells. Moreover, AngII could directly activate infiltrating immunocompetent cells, including chemotaxis, differentiation and proliferation. Recent data also suggest that RAS activation could play a certain role even in immunologically-induced inflammation. Transcriptional regulation, predominantly via nuclear factor-κB (NF-κB) and AP-1 activation, and second mediator systems, such as endothelin-1, the small G protein (Rho) and redox-pathways are shown to be involved in the molecular mechanism by which AngII exerts those functions. Finally, AngII participates in tissue repair and remodeling, through the regulation of cell growth and matrix synthesis. In summary, recent data support the hypothesis that RAS is key mediator of inflammation. Further understanding of the role of the RAS in this process may provide important opportunities for clinical research and treatment of inflammatory diseases.

Section snippets

Alteration of vascular permeability by RAS

Local increase of vascular permeability resulting in cell infiltration and exudation of protein-rich fluid is the most important event in the initial phase of the inflammation (Michell & Cotran, 1999).

RAS effects on cell adhesion and chemotaxis of inflammatory cells

A critical step in the inflammatory response is the leukocyte extravasation, from lumen to the interstitial tissue, that can be divided as follows: (1) cell margination (rolling and adhesion); (2) transmigration; and (3) migration toward chemotactic stimuli (Michell & Cotran, 1999).

Modulation of tissue repair by RAS via cellular and connective tissue replacement

Tissue repair is the most important outcome of the inflammatory response and involves two distinct processes: (1) regeneration, denoting the replacement of injured cells by cells of the same type; and (2) replacement by connective tissue, called fibrosis, which causes a permanent scar (Michell & Cotran, 1999).

Conclusion

In this paper we review the multifunctional properties of AngII (local RAS) acting on alteration of hemodynamics and vascular permeability, expression of adhesion molecules, chemotaxis for leukocytes, activation of vascular pericytes, and repair via cellular growth and matrix synthesis. Most of such apparently random biological pictures can be discussed within the context of inflammation. Potential mechanisms by which AngII exerts a wide variety of effector functions may be in part due to

Acknowledgements

The author’s papers cited in this review have been supported by grants from Japan Health Science Foundacion, Juntendo University Alumni Association, Fondo de Investigación Sanitaria FIS (98/3143, 99/3016, 01/3130, 01/0605), Comunidad Autónoma de Madrid (08.4/0017/2000, 08.9/002/2000, 98/083/0002, 08.9/0002/2001), Ministerios de Educación y Ciencia y tecnologı́a (PM97/0085; SAF 2001/0717), Sociedad Española de Nefrologı́a, Fundación Renal Iñigo Alvarez de Toledo and European grant

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