Recent Advances in the Endogenous Brain Renin-Angiotensin System and Drugs Acting on It

Figure 2

Function of angiotensin receptors in central nervous system-related disorders. Overview of brain RAS demonstrating the formation of its component in periphery and in the CNS. The diagram represents the specific converting enzymes involved for the conversion AGT to Ang IV, their receptors, and their role in various CNS disorders and protection. The RAS pathway initiates by conversion of angiotensinogen from the liver to Ang I in the lungs by sequential action of enzymes and prorenin-renin which also acts on a specific prorenin receptor. Ang I in the presence of ACE is further converted to Ang II, which gets fragmented into biological active form Ang III and IV which further acts on AT1, AT2, AT4, and MasR. The AT1 activation results in stress, neuroinflammation, and stroke. This effect is counteracted by the Ang II/AT2R and Ang (1-7)/MasR signaling pathway resulting in decrease in inflammatory cytokines and reduced ROS contributing to neuroprotection and cell proliferation. Specific inhibitors like ARBs, ACEI, and renin inhibitors have demonstrated to improve the pathological conditions. Abbreviations: Ang I: angiotensin I; Ang II: angiotensin II; Ang III: angiotensin III; Ang IV: angiotensin IV; ACE: angiotensin-converting enzyme; ACE 2: angiotensin-converting enzyme; APA: aminopeptidase A; APB: aminopeptidase B; APN: aminopeptidase N; MasR: Mas receptor; AT1: angiotensin receptor subtype 1; AT2: angiotensin receptor subtype 2; AT4: angiotensin receptor subtype 4; PD: Parkinson’s disease; AD: Alzheimer’s disease.