What have we learned about the kallikrein-kinin and renin-angiotensin systems in neurological disorders?

Figure 3 Schematic representation of the renin-angiotensin system and its physiopathological effects. Ang II may be generated in the brain via the classical pathway, through renin and angiotensin converting enzyme (ACE) action (through Ang I cleavage) or can be directly released from angiotensinogen by cathepsin G or tonin actions. Ang1-7 is active in several organs including the brain and several endopeptidases such as thimet oligopeptidase (TOP) or neutral endopeptidases (NEP) may metabolize Ang I, generating Ang1-7. AngII may also be hydrolyzed by ACE2 to generate Ang1-7. Binding to Ang II type 1 receptor (AT1R), Ang II stimulates vasoconstriction, aldosterone and steroid hormones release, which are involved in sodium reabsorption and water retention. AT1R activity is also related to hypertension, heart dysfunction, brain ischemia, abnormal stress responses, blood-brain barrier breakdown and inflammation. The second receptor involved in Ang II activity is AT2R and is expressed during fetal development, decreasing after birth and remaining at a low concentration during adulthood. It has been linked to cell proliferation, differentiation, apoptosis and the regeneration of several tissues. Ang1-7 is a Mas receptor agonist, which is related to neuronal plasticity and changes in cellular phenotype that are produced by neuronal activity such as synaptic rearrangements and mossy fiber sprouting in the hippocampus.