Renin–Angiotensin–Aldosterone System: Friend or Foe—The Matter of Balance. Insight on History Therapeutic Implications and COVID-19 Interactions

摘要

The renin–angiotensin–aldosterone system (RAAS) ranks among the most challenging puzzles in cardiovascular medicine. It participates in the principal homeostatic mechanisms such as regulation of vascular tone, circulating volume, organ perfusion, blood clotting, cardiomyocyte growth and collagen matrix turnover [1,2]. The RAAS is a well-established player in the acute stress reaction, with renin occupying the eminent position. Its crucial role is underscored by a variety of triggering stimuli such as renal hypoperfusion due to hypotension, renal artery narrowing or sympathetic system-induced vasoconstriction or reduced sodium chloride (NaCl) load near the macula densa—all issues triggering renin production via different but interdependent routes. This guarantees that the RAAS is “a friend in need—a friend indeed”. On the other hand, if chronically activated, increased angiotensin II (Ang II) and aldosterone levels in the circulation and tissues result in oxidative overload and chronic inflammation followed by endothelium dysfunction, energy imbalance and fibrocyte proliferation. The results of these processes are the undesirable remodeling of the heart, kidney, brain and vessels. Inappropriate RAAS stimulation is considered to underlie a number of pathologic conditions including hypertension, atherosclerosis complications, heart and kidney failure, mental disturbances and inflammatory damage including acute respiratory distress syndrome (ARDS). Besides Ang II and aldosterone, the RAAS involves a bulk of other biologically active molecules involved in a number of physiological and pathological processes, whose role remains to be elucidated [3,4,5,6,7].