Alternate Angiotensin II-Forming Pathways and Their Importance in Physiological or Physiopathological Conditions

For a long time, the renin-angiotensin-aldosterone system was considered a component of the endocrine system because angiotensin II, the main effector of this system was thought to be generated exclusively in blood, thereafter being distributed to all organs and tissues by the blood flow and becoming active on those targets that possessed the appropriate receptors for this peptide. Recently though, this model had to be revised, because it was discovered that all the components of this system, particularly angiotensinogen, renin, and angiotensins I and II, can also be locally produced in several organs and tissues 1,2 . Since this discovery, angiotensin II has also been considered a peptide with paracrine, autocrine, or both paracrine and autocrine action in several places in an organism. Thus the concept was established of the existence of several renin-angiotensin systems distributed throughout different organs (heart, blood vessels, adrenal marrow, central nervous system, and others), whose actions complement those of the classical renin-angiotensin-aldosterone system. The importance of these local renin-angiotensin systems seems to be related to the fact that they may have a direct effect on local regulation mechanisms. This direct effect may contribute to a great number of slower progressing, yet longer lasting, tissue homeostasis mechanisms, such as cell growth, the formation of tissue matrix, vascular proliferation, endothelium function modulation, and the control of the apoptosis process, particularly during embryonic development.