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

Figure 1 Schematic representation of the kallikrein-kinin system. Bradykinin and Lys-bradykinin (BK), generated by the action of plasma or tissue kallikrein on the precursor (high or low molecular weight kininogen) are the main bradykinin and its receptor (B2R) agonists. These peptides can be converted to B1R agonists after removal of C-terminal-Arg. Both peptidases, membrane-bound carboxypeptidase M, linked to B1R at the C-terminal domain or the soluble carboxypeptidase N are able to remove Arg from the C-terminal portion of BK. B2R is constitutively expressed, showing physiological effects such as vasodilation, transient nitric oxide (NO) production by endothelial nitric oxide synthase (eNOS), whereas B1R expression is induced by injury or inflammatory conditions, with long-lasting NO production, resulting in a neurotoxic environment with reactive oxygen species (ROS) production and increased release of glutamate with excitoxicity-induced neuronal death.