Angiotensin, inflammation, hypertension, and cardiovascular disease

Abstract

We are used to thinking of angiotensin (Ang) II as a regulatory hormone that stimulates constriction of vascular smooth muscle cells, aldosterone release from the adrenal gland, and sodium reabsorption in the renal tubule. We have also become accustomed to understanding that Ang II may be formed and may act locally as a chemokine that induces tyrosine phosphorylation, cell growth, hypertrophy, and differentiation. Viewing Ang II as an inflammatory molecule is stranger still. Nevertheless, recent evidence shows that Ang II is important in stimulating the production of reactive oxygen species and the activation of ancient inflammatory mechanisms. The nuclear factor kappaB (NF-kappaB) is pivotal to these processes. Activation of NF-kappaB stimulates the expression of a gene menagerie that is important to chemoattraction, expression of surface adhesion molecules, coagulation, and inflammation. In addition, Ang II has been shown to regulate cellular immune responses. It stimulates the proliferation of lymphocytes and contributes to their activation via calcineurin-related pathways. Knowledge of these mechanisms may provide additional therapeutic avenues.