Neuronal Angiotensin

Many tissues, including the brain, contain all components of the renin–angiotensin system and generate angiotensin peptides independent of the systemic, circulating system. Within the brain renin, some questions remain as to how the precursor, angiotensinogen, and its processing enzymes interact to produce the active compounds, angiotensin II/III, because they are rarely localized to the same brain nucleus let alone the same cell. These questions aside, there is clear evidence for actions of angiotensin peptides in regions behind the blood–brain barrier. Receptors for angiotensin peptides, including AT(1) and AT(2) receptors, are distributed in a characteristic pattern throughout the brain, with many of these sites behind the blood–brain barrier. Stimulation of these receptors affects multiple physiological functions – actions which often complement the physiological roles established for the systemic renin–angiotensin system. These include effects on fluid and electrolyte homeostasis, autonomic and neuroendocrine regulation, and modulation of sensory function. Moreover, administration of selective receptor antagonists attenuates several of these functions when they are activated in response to physiological stimuli, such as dehydration. Together, these observations point to important roles for brain-derived angiotensin peptides in a wide range of physiological functions.