Angiotensin receptor binding in human hypothalamus: autoradiographic localization

McKinley, Michael J.; Allen, Andrew M.; Clevers, J.C.; Paxinos, George; Mendelsohn, Frederick A.O.

doi:10.1016/0006-8993(87)91260-1

Cited by 72 publications

(28 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Initially, in vitro autoradiographic binding techniques were used to map the distribution of these receptors in the brains of several mammalian species, including humans [9][10][11][12][13]. These investigations revealed that many of the sites in the CNS that contained high levels of angiotensin receptors were regions that played important roles in the regulation of body fluid and electrolyte homeostasis and of the cardiovascular system (Fig.…”

Section: Angiotensin Receptorsmentioning

confidence: 99%

Brain Angiotensin and Body Fluid Homeostasis.

McKinley

Allen²,

Mathai³

et al. 2001

JJP

View full text Add to dashboard Cite

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...

show abstract

Section: Angiotensin Receptorsmentioning

confidence: 99%

Brain Angiotensin and Body Fluid Homeostasis.

McKinley

Allen²,

Mathai³

et al. 2001

JJP

View full text Add to dashboard Cite

show abstract

“…The interaction between exogenously administered ANG II and sodium valproate might be supposed not only at places located outside the blood-brain barrier (BBB), such as the me dian eminence and the posterior pituitary, but also in OT-secreting structures located inside the BBB. In fact, even though circulating ANG II is unable to cross the BBB [32], ANG II is thought to bind receptors in the circumventricular organs [33][34][35]. These structures are located outside the BBB [36], but they are connected with AVP and OT neurons in the supraoptic and para ventricular nuclei.…”

Section: Discussionmentioning

confidence: 99%

Different Effects of the GABAergic Agent Sodium Valproate on the Oxytocin Responses to Angiotensin II and Insulin-Induced Hypoglycemia in Normal Men

Chiodera¹,

Coiro

1991

Horm Res

View full text Add to dashboard Cite

The present study was performed in order to establish whether angiotensin II (ANG II) and/or insulin-induced hypoglycemia exert their oxytocin (OT)-releasing effects by interacting with a GABAergic pathway. For this purpose, in 14 normal men the OT responses to ANG II (infusion for 60 min of successively increasing doses of 4, 8 and 16 ng/kg·min, each dose for 20 min; n = 7) or to insulin (0.15 IU/kg)-induced hypoglycemia (n = 7) were evaluated with or without previous treatment with the GABAergic agonist sodium valproate (600 mg in 3 divided doses, p.o.). In all subjects insulin produced a similar hypoglycemic response regardless of sodium valproate administration. Both ANG II and insulin-induced hypoglycemia produced significant increases in plasma OT levels (mean peaks were about 60% higher than baseline). The pretreatment with sodium valproate was unable to change the OT response to hypoglycemia, whereas it abolished the ANG-II-induced OT rise. These data suggest that in man a GABAergic mechanism is involved in the regulation of the OT response to ANG II, but not in the mediation of poglycemia-induced OT release.

show abstract

“…Ang II receptors are localized in distinct brain nuclei [3,20,22] which show a good correlation with the distribution of Ang II immunoreactivity [18] and physiological responses to Ang II [15], This system may be involved in the regulation of fluid and electrolyte ho meostasis, since Ang II has a number of striking central actions including stimulation of drinking, salt appetite, neurogenically mediated hypertension and release of both anterior and poste rior pituitary hormones [26]. Areas subserving these actions in the rostral forebrain include the OVLT and the intervening tis sue of the lamina terminalis including the MnPO [26].…”

Section: Discussionmentioning

confidence: 99%

“…Ang II receptor binding was measured by quantitative in vitro auto radiography as previously described [3,20,22]. Briefly, serial cryostat sections (20 pm) of forebrain and hindbrain were cut in the coronal plane, thaw-mounted onto gelatin-coated slides, dried in a dessicator at 4 °C overnight under reduced pressure and stored at -8 0 °C in sealed boxes with silica gel.…”

Section: Methodsmentioning

confidence: 99%

“…These results suggest that only a limited subset of brain Ang II receptors respond to sodium deprivation and do so in a region-specific manner. These results support evidence that the central angiotensin system may contribute to the regulation of f uid and electrolyte homeostasis.Receptor binding sites for angiotensin II (Ang II) in the brain are located in discrete sites with a unique pattern of distri bution [3,20,22]. Those associated with the circumventricular organs are accessible to blood-borne Ang II [37], because of the absence of the blood-brain barrier [29]; however in other sites, the receptors are related to intrinsic angiotensin-containing neural elements [ 18], Central administration of Ang II induces drinking, in creased salt appetite, a rise in blood pressure and vasopressin release suggesting a role for brain Ang II in regulating car diovascular and body fluid homeostasis [26], Ang II receptors in the peripheral tissues are modulated by changes in sodium intake.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Angiotensin II Receptor Binding in the Rat Hypothalamus and Circumventricular Organs during Dietary Sodium Deprivation

Yamada

Mendelsohn²

1989

Neuroendocrinology

View full text Add to dashboard Cite

The effect of dietary sodium intake on angiotensin II (Ang II) receptor binding in the rat brain was studied using quantitative in vitro autoradiography. After 2 weeks of sodium deprivation, the peripheral angiotensin system was activated as shown by increased plasma renin activity (4-fold) and plasma aldosterone concentration (approximately 40-fold). At the same time, Ang II receptor binding in the adrenal glomerulosa zone increased by 40%. Frozen brain sections prepared from 12 male Sprague-Dawley rats (6 control, 6 sodium-deprived) were incubated with ¹²⁵I [Sar¹, He⁸] Ang II, exposed to X-ray film, and Ang II receptor binding in individual brain nuclei was quantitated by computerized densitometry. Ang II binding in the area postrema was significantly suppressed in the sodium-deprived rats (60% of control; p < 0.05). No change was observed in the other circumventricular organs studied, the subfomical organ or organum vasculosum of the lamina terminalis. Ang II binding in the solitary tract nucleus was not affected by the dietary salt treatment. In the hypothalamic paraventricular nucleus, there was a small (9%) but significant (p < 0.001) increase in Ang II receptor binding in the sodium-deprived group. However, no change was observed in the hypothalamic median preoptic or suprachiasmatic nuclei, areas with similarly high Ang II receptor binding. These results suggest that only a limited subset of brain Ang II receptors respond to sodium deprivation and do so in a region-specific manner. These results support evidence that the central angiotensin system may contribute to the regulation of fluid and electrolyte homeostasis.

show abstract

Angiotensin receptor binding in human hypothalamus: autoradiographic localization

Cited by 72 publications

References 19 publications

Brain Angiotensin and Body Fluid Homeostasis.

Brain Angiotensin and Body Fluid Homeostasis.

Different Effects of the GABAergic Agent Sodium Valproate on the Oxytocin Responses to Angiotensin II and Insulin-Induced Hypoglycemia in Normal Men

Angiotensin II Receptor Binding in the Rat Hypothalamus and Circumventricular Organs during Dietary Sodium Deprivation

Contact Info

Product

Resources

About