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)