The Renin-Angiotensin System (RAS)
RAS is a complex cascade event that plays an important role in the control of hydrosaline homeostasis, blood pressure and plasma volume. The cascade begins with renin splitting angiotensinogen, a peptide produced in the liver, into an inactive decapeptide, angiotensin I (Ang I). The latter is converted to the active form by another proteolytic enzyme, the angiotensin II conversion enzyme (ACE) produced in the capillary endothelium where it converts angiotensin I (decapeptide) to angiotensin II (Ang II, octapeptide), a powerful vasoconstrictor. ACE, in addition to decoupling Ang I to Ang II, has another important function, it degrades bradykinin into inactive fragments. Bradykinin produces vasodilation through the production of prostaglandins and nitric oxide (NO) and inhibits the proliferation of smooth vascular muscle.
At the cellular level Ang II modulates cell contraction, cell growth, differentiation and apoptosis; it can promote the production of other cytokines, the expression of adhesion molecules and the subsequent recovery of inflammation cells, chemotaxis, macrophage activation. It has a proinflammatory action. The tissue increase of Ang II formation induces inflammation and Ang II is itself a powerful pro-inflammatory cytokine as well as a growth factor. Scientific evidence shows that Ang II activates the transcriptional factor NF-kb, the key factor of nuclear transcription in inflammatory and fibrotic diseases, and its activation allows the transcription of several inflammatory genes, including interleukin 6 and IL-1 which are responsible for the cytokinic cascade and the hyperactive inflammatory state that is generated especially in the third stage of infection. (10-11-12-13)