Brain Angiotensin and Body Fluid Homeostasis.

Abstract

The circulating hormone angiotensin II is an important humoral factor regulating cardiovascular and body fluid and electrolyte homeostasis. Potent direct constrictor actions on the vasculature, stimulation of the sodium-retaining hormone aldosterone from the adrenal cortex, generation of thirst and sodium appetite, release of the urine-concentrating hormone vasopressin, intrarenal regulation of tubular-glomular balance, and feedback inhibition of renal renin release are just some of the well recognized actions of this circulating octapeptide. But angiotensin II may have further roles in regulating body fluid homeostasisnot as a blood-borne hormone, but as a neuropeptide generated within the central nervous system (CNS), where it may act as a neurotransmitter or modulator of neural function to influence thirst, vasopressin secretion, renin release, sodium excretion, and body temperature. Localization of an Angiotensinergic System in the Brain and Spinal Cord AngiotensinogenDuring the past 25 years, much evidence has emerged that supports the view that angiotensin II and its active metabolites are generated in the brain from centrally synthesized angiotensinogen. The principle Key words: angiotensin, AT 1 receptors, sodium, osmoregulation, thermoregulation.Abstract: 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 p...

Apela Regulates Fluid Homeostasis by Binding to the APJ Receptor to Activate Gi Signaling

“…Early studies demonstrated the role of this GPCR subfamily in fluid homeostasis. Treatment with angiotensin II in mice inhibits drinking of water or saline, whereas administration of angiotensin II receptor antagonists stimulates diverse responses including water drinking, vasopressin secretion, and natriuresis (31,32). In addition, experiments on dogs showed that bradykinin regulates proximal tubular sodium reabsorption (33).…”

Central angiotensin II receptors mediate hemodynamic response variability to stressors

“…ANG II produces an increase in arterial pressure due to both a direct vasoconstrictor effect, mediated by AT 1 receptors in blood vessels, and a central sympathoexcitatory effect. Peripheral ANG II binds to receptors in the circumventricular organs of the brain, including the organum vasculosum of the lamina terminalis and the subfornical organ (29). These sites, in turn, send projections to several other nuclei that activate the sympathetic nervous system, increasing arterial pressure and regulating fluid balance.…”

“…There also is evidence of a central renin-angiotensin system (RAS) that contributes to stress responses (6,23,41). Endogenous ANG II can be found in numerous periventricular locations (29), and ANG II receptors (both AT 1 and AT 2 ) are located within the hypothalamus, brain stem, and pituitary (45). The central RAS also has been implicated in long-term regulation of arterial pressure and the etiology of hypertension (3,35,36,42).…”

Interaction between Dopaminergic and Angiotensinergic Systems on Thirst in Adult Male Rats

“…It is generally accepted that the central angiotensin II-induced cardiovascular and endocrine responses such as induction of drinking and dipsogenic effects, pressor response and release of AVP are mediated by AT 1 receptors [25,18]. Furthermore, central injection of AT 1 receptor antagonist, Losartan, blocks AT 1 receptors and influences on central angiotensin mechanisms [24,26]. Infusion of Ang II into a lateral cerebral ventricle produce an increase in blood pressure [27,20,28], increase in mean arterial pressure [29,30], decrease in urine flow [27], regulate hydromineral balance [22], induce the pressor response [31], stimulate AVP and OT release [20,28] and elevate RSNA (renal sympathetic nerve activity) [32].…”