Brain angiotensin and body fluid homeostasis

Angiotensinogen, the precursor molecule of the peptides angiotensin I, II, and III, is synthesized in the brain and the liver. Evidence is reviewed that angiotensin II, and possibly angiotensin III, that are generated within the brain act within neural circuits of the central nervous system to regulate body fluid balance. Immunohistochemical studies in the rat brain have provided evidence of angiotensin-containing neurons, especially in the hypothalamic paraventricular nucleus, subfornical organ, periventricular region, and nucleus of the solitary tract, as well as in extensive angiotensin-containing fiber pathways. Angiotensin immunoreactivity is observed by electron microscope in synaptic vesicles in several brain regions, the most prominent of these being the central nucleus of the amygdala. Neurons in many parts of the brain (lamina terminalis, paraventricular and parabrachial nuclei, ventrolateral medulla, and nucleus of the solitary tract) known to be involved in the regulation of body fluid homeostasis exhibit angiotensin receptors of the AT(1) subtype. Pharmacological studies in several species show that intracerebroventricular administration of AT(1) receptor antagonist drugs inhibit homeostatic responses to the central administration of hypertonic saline, intravenous infusion of the hormone relaxin, or thermal dehydration. Responses affected by centrally administered AT(1) antagonists are water drinking, vasopressin secretion, natriuresis, increased arterial pressure, reduced renal renin release, salt hunger, and thermoregulatory adjustments. We conclude that angiotensinergic neural pathways in the brain probably have an important homeostatic function, especially in regard to osmoregulation and thermoregulation, and the maintenance of arterial pressure.