Angiotensin II receptors in SFO but not in OVLT mediate isoproterenol-induced thirst

1994 ◽  
Vol 267 (1) ◽  
pp. R7-R15 ◽  
Author(s):  
D. A. Fitts
Keyword(s):  
Angiotensin Ii ◽  
Circumventricular Organs ◽  
Ang Ii ◽  
Circumventricular Organ ◽  
Adrenergic Agonist ◽  
Receptor Sites ◽  
Organum Vasculosum Laminae Terminalis ◽  
Reduced Drinking ◽  
Beta Adrenergic Agonist ◽  
The Brain

Thirst elicited by the beta-adrenergic agonist isoproterenol in rats depends in part on the secretion of renin, the consequent synthesis of angiotensin II (ANG II), and the binding of circulating ANG II to dipsogenic receptors in the brain. These receptors probably reside in either of two forebrain circumventricular organs, the subfornical organ (SFO) or organum vasculosum laminae terminalis (OVLT). Experiments determined that lesions of the SFO, but not of the OVLT, reduced drinking induced by isoproterenol treatment. Competitive ANG II-receptor antagonism with sarthran reduced isoproterenol-induced drinking when the blocker was infused into the SFO but not when it was infused into the OVLT or into the lateral ventricles at a 25-fold greater dose. The findings confirm the widely held belief that renin-dependent thirst elicited by isoproterenol relies on ANG II binding to receptor sites at a circumventricular organ in the brain. The results demonstrate that this site is the SFO and not the OVLT.

Release of immunoreactive angiotensin II from neuronal cultures: adrenergic influences

1989 ◽  
Vol 257 (3) ◽  
pp. C588-C595 ◽  
Author(s):  
E. M. Richards ◽  
K. Hermann ◽  
C. Sumners ◽  
M. K. Raizada ◽  
M. I. Phillips
Keyword(s):  
Angiotensin Ii ◽  
Neuronal Cultures ◽  
Ang Ii ◽  
Adrenergic Agonist ◽  
Adrenergic Antagonist ◽  
Glial Cultures ◽  
Basal Release ◽  
Adrenergic Blocker ◽  
Beta Adrenergic Agonist ◽  
Glial Cell Cultures

The effects of adrenergic drugs on the release of immunoreactive angiotensin II (ANG II-ir) from brain cells in culture were examined. In neuronal cultures, basal release of Ang II-ir was 43.65 +/- 7.44 pg/5-min incubation period (n = 14 experiments; 52 individual determinations), and in astrocytic glial cultures, it was 21.76 +/- 5.7 pg (n = 8 experiments; 24 individual determinations) when cells were exposed to buffer alone. Incubation of neuronal cultures with the alpha 2-adrenergic antagonist yohimbine (0.1-50 microM, 5 min) caused concentration-dependent increases in ANG II-ir release above basal levels. Analysis of the released material by high-pressure liquid chromatography revealed that authentic ANG II was present. No increase in the release of ANG II-ir was seen from glial cells. Experiments using neuronal cultures revealed that the yohimbine-induced release of ANG II-ir may be secondary to increased norepinephrine (NE) release. Incubation of neuronal cultures with NE (10 nM-50 microM) caused concentration-dependent increases in the release of ANG II-ir. This effect of NE was not inhibited by the alpha 1-adrenergic blocker prazosin. However, a weaker release of ANG II-ir from neuronal cultures was stimulated by the beta-adrenergic agonist isoproterenol at 100 microM. These data show that ANG II-ir can be released from neuronal but not glial cell cultures by adrenergic receptor-mediated mechanisms.

Actions of angiotensin II on the brain: mechanisms and physiologic role

1984 ◽  
Vol 246 (5) ◽  
pp. F533-F543 ◽  
Author(s):  
I. A. Reid
Keyword(s):  
Angiotensin Ii ◽  
Large Body ◽  
Renin Angiotensin System ◽  
Circumventricular Organs ◽  
Acth Stimulation ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Arterial Blood ◽  
Receptor Sites ◽  
The Brain

Angiotensin II acts on the brain to produce a variety of effects including elevation of arterial blood pressure, increased release of vasopressin and ACTH, stimulation of drinking and sodium appetite, and natriuresis. Many, and possibly all, of these effects can be produced by centrally administered angiotensin II or by circulating angiotensin II, which appear to act at common receptor sites located in the circumventricular organs. Whether these effects are normally produced by blood-borne angiotensin II formed by the renal renin-angiotensin system, by angiotensin II formed centrally by the putative brain renin-angiotensin system, or by both, remains to be determined. A large body of information concerning the site and mechanism of these different central actions of angiotensin II is available, and the physiologic significance of these actions is beginning to be understood. Nevertheless, much additional research will be required before the actions of angiotensin II on the brain are completely understood.

Central effects of catecholamine antagonists on angiotensin-induced vasopressin secretion in conscious rats

1988 ◽  
Vol 118 (1) ◽  
pp. 82-88 ◽  
Author(s):  
Ken'ichi Yamaguchi ◽  
Takeo Karakida ◽  
Mamoru Koike ◽  
Hitoshi Hama
Keyword(s):  
Angiotensin Ii ◽  
Ang Ii ◽  
Adrenergic Agonist ◽  
Beta Adrenergic ◽  
Central Effects ◽  
Conscious Rats ◽  
Vasopressin Secretion ◽  
Beta Adrenergic Agonist ◽  
Alpha Antagonist ◽  
Alpha Adrenergic Agonist

Abstract. To evaluate the roles for catecholamines in angiotensin II (ANG II)-induced vasopressin (AVP) release, we examined in conscious rats the effects of intraventricular (ivt) administrations of catecholamine antagonists on plasma AVP responses to ivt applications of its agonists and ANG II. Plasma AVP was determined by RIA using trunk blood collected after decapitation. Dopamine (0.15 μmol), phenylephrine (an alpha-adrenergic agonist, 0.15 μmol) or ANG II (48.2 pmol) augmented plasma AVP 90 sec after the injection, whereas after isoproterenol (a beta-adrenergic agonist, 0.15 μmol) plasma AVP was unaffected. The plasma AVP responses to both dopamine and ANG II were significantly (P < 0.01) inhibited by haloperidol (a dopamine blocker, 0.15 μmol) given 10 min before administration of these agents. Pre-administration of phenoxybenzamine (an alpha antagonist, 0.15 μmol) which was confirmed to abolish the effect of phenylephrine, or propranolol (a beta antagonist, 0.15 μmol) did not block the effect of ANG II. Administration of haloperidol, phenoxybenzamine or propranolol alone was without effect on plasma AVP level. On the basis of these results, we concluded that ANG II-induced AVP secretion may be mediated and/or modulated by dopamine.

Influnce of the beta-adrenergic agonist clenbuterol on plasma catecholamines and lymphocyte beta-receptors

1986 ◽  
Vol 1 (3) ◽  
pp. 234-236
Author(s):  
B. Bondy ◽  
M. Ackenheil ◽  
G. Laakmann ◽  
H.T. Munz
Keyword(s):  
Specific Binding ◽  
Plasma Catecholamines ◽  
Adrenergic System ◽  
Plasma Norepinephrine ◽  
Adrenergic Agonists ◽  
Adrenergic Agonist ◽  
Beta Receptors ◽  
Β Receptor ◽  
Beta Adrenergic Agonist ◽  
The Brain

SummaryThe influence of subchronic application of the β-adrenergic agonist clenbuterol on plasma norepinephrine (NE), epinephrine (E) and β-receptors on lymphocytes was investigated in 8 male, healthy volunteers. Treatment with clenbuterol (0.04 mg/day) for 6 days induced significant reduction of β-receptor specific binding in 7 of the 8 subjects with a mean decrease of 40% (p < 0.01) with no changes in affinity. Concomitantly an increase in the plasma NE concentration was observed (mean 50%, p < 0.01), but no significant overall alteration of E concentration. Our results suggest that β-adrenergic agonists exercise a similar effect on the peripheral adrenergic system and on the adrenergic system in the brain.

scholarly journals Update on angiotensin II: new endocrine connections between the brain, adrenal glands and the cardiovascular system

2017 ◽  
Vol 6 (7) ◽  
pp. R131-R145 ◽  
Author(s):  
Frans H H Leenen ◽  
Mordecai P Blaustein ◽  
John M Hamlyn
Keyword(s):  
Angiotensin Ii ◽  
Sympathetic Activity ◽  
Endocrine Function ◽  
Lv Function ◽  
Slow Pathway ◽  
Ang Ii ◽  
Endogenous Ouabain ◽  
Plasma Angiotensin ◽  
Synthase Inhibitor ◽  
The Brain

In the brain, angiotensinergic pathways play a major role in chronic regulation of cardiovascular and electrolyte homeostasis. Increases in plasma angiotensin II (Ang II), aldosterone, [Na+] and cytokines can directly activate these pathways. Chronically, these stimuli also activate a slow neuromodulatory pathway involving local aldosterone, mineralocorticoid receptors (MRs), epithelial sodium channels and endogenous ouabain (EO). This pathway increases AT1R and NADPH oxidase subunits and maintains/further increases the activity of angiotensinergic pathways. These brain pathways not only increase the setpoint of sympathetic activity per se, but also enhance its effectiveness by increasing plasma EO and EO-dependent reprogramming of arterial and cardiac function. Blockade of any step in this slow pathway or of AT1R prevents Ang II-, aldosterone- or salt and renal injury-induced forms of hypertension. MR/AT1R activation in the CNS also contributes to the activation of sympathetic activity, the circulatory and cardiac RAAS and increase in circulating cytokines in HF post MI. Chronic central infusion of an aldosterone synthase inhibitor, MR blocker or AT1R blocker prevents a major part of the structural remodeling of the heart and the decrease in LV function post MI, indicating that MR activation in the CNS post MI depends on aldosterone, locally produced in the CNS. Thus, Ang II, aldosterone and EO are not simply circulating hormones that act on the CNS but rather they are also paracrine neurohormones, locally produced in the CNS, that exert powerful effects in key CNS pathways involved in the long-term control of sympathetic and neuro-endocrine function and cardiovascular homeostasis.

scholarly journals Central interactions of aldosterone and angiotensin II in aldosterone- and angiotensin II-induced hypertension

2011 ◽  
Vol 300 (2) ◽  
pp. H555-H564 ◽  
Author(s):  
Baojian Xue ◽  
Terry G. Beltz ◽  
Yang Yu ◽  
Fang Guo ◽  
Celso E. Gomez-Sanchez ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Oxidase Inhibitor ◽  
Male Rats ◽  
Ang Ii ◽  
Adeno Associated Virus ◽  
Synergistic Interactions ◽  
Induced Hypertension ◽  
Ros Scavenger ◽  
The Brain

Many studies have implicated both angiotensin II (ANG II) and aldosterone (Aldo) in the pathogenesis of hypertension, the progression of renal injury, and cardiac remodeling after myocardial infarction. In several cases, ANG II and Aldo have been shown to have synergistic interactions in the periphery. In the present studies, we tested the hypothesis that ANG II and Aldo interact centrally in Aldo- and ANG II-induced hypertension in male rats. In rats with blood pressure (BP) and heart rate (HR) measured by DSI telemetry, intracerebroventricular (icv) infusions of the mineralocorticoid receptor (MR) antagonists spironolactone and RU28318 or the angiotensin type 1 receptor (AT1R) antagonist irbesartan significantly inhibited Aldo-induced hypertension. In ANG II-induced hypertension, icv infusion of RU28318 significantly reduced the increase in BP. Moreover, icv infusions of the reactive oxygen species (ROS) scavenger tempol or the NADPH oxidase inhibitor apocynin attenuated Aldo-induced hypertension. To confirm these effects of pharmacological antagonists, icv injections of either recombinant adeno-associated virus carrying siRNA silencers of AT1aR (AT1aR-siRNA) or MR (MR-siRNA) significantly attenuated the development of Aldo-induced hypertension. The immunohistochemical and Western blot analyses of AT1aR-siRNA- or MR-siRNA-injected rats showed a marked reduction in the expression of AT1R or MR in the paraventricular nucleus compared with scrambled siRNA rats. When animals from all studies underwent ganglionic blockade with hexamethonium, there was a smaller reduction in the fall of BP in animals receiving icv AT1R or MR antagonists. These results suggest that ANG II and Aldo interact in the brain in a mutually cooperative manner such that the functional integrity of both brain AT1R and MR are necessary for hypertension to be induced by either systemic ANG II or Aldo. The pressor effects produced by systemic ANG II or Aldo involve increased central ROS and sympathetic outflow.

17β-Estradiol inhibits angiotensin II activation of area postrema neurons

2003 ◽  
Vol 285 (4) ◽  
pp. H1515-H1520 ◽  
Author(s):  
Jaya Pamidimukkala ◽  
Meredith Hay
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Area Postrema ◽  
Ang Ii ◽  
Circumventricular Organ ◽  
Ici 182,780 ◽  
Central Neurons ◽  
Total Inhibition ◽  
17Β Estradiol ◽  
Vasoactive Peptide

It is well established that the area postrema, as a circumventricular organ, is susceptible to modulation by circulating hormones and peptides. Furthermore, activation of the area postrema has been shown to modulate central neurons involved in the regulation of cardiovascular function and blood pressure. In particular, the vasoactive peptide angiotensin II (ANG II) has been shown to inhibit baroreflex regulation of heart rate and increase sympathetic outflow and blood pressure via activation of area postrema neurons. Estrogen is thought to protect against hypertension in both humans and animal models and has been shown in a number of systems to alter the effects of ANG II. The purpose of the present study was to determine the effects of estrogen on ANG II activation of area postrema neurons. In this study, the effects of ANG II and KCl on fura 2-measured cytosolic Ca2+ concentration ([Ca2+]i) responses in cultured area postrema neurons in the presence and absence of 12-h exposure to 100 nM 17β-estradiol (E2) were evaluated. In neurons incubated in control vehicle media, 50 nM ANG II increased [Ca2+]i by 92 ± 12%. In neurons preincubated with 100 nM E2, ANG II increased [Ca2+]i by only 68 ± 11%, for a total inhibition of the ANG II-evoked response of 24%. Coapplication of the estrogen receptor antagonist ICI-182,780 did not inhibit the effects of E2. In the same cells in which the effects of E2 on ANG II-evoked responses were tested, the effects of incubation in E on the depolarization-induced increased [Ca2+2]i due to 60 mM KCl were also tested. Incubation of the cells with 100 nM E increased the KCl-evoked [Ca2+2]i response, and this response was blocked by ICI-182,780. These results suggest that in the area postrema, estrogen may utilize multiple pathways to modulate neural activity and responses to ANG II.

Respiratory Control During Exercise: Hormones, Osmolality, Strong Ions, and Paco2

1994 ◽  
Vol 19 (3) ◽  
pp. 334-349 ◽  
Author(s):  
Donald B. Jennings
Keyword(s):  
Angiotensin Ii ◽  
Respiratory Control ◽  
Circumventricular Organs ◽  
Strong Ion Difference ◽  
Concentration Difference ◽  
Peripheral Tissues ◽  
Central Chemoreceptors ◽  
Central Chemoreception ◽  
Increasing Temperature ◽  
The Brain

For optimal performance of exercising muscle, the charge state of proteins must be maintained; the pH environment of protein histidine imidazole groups must be coordinated with their pK. During exercise, increasing temperature and osmolality as well as changes in strong ions affect the pK of imidazole groups. Production of strong organic anions also decreases the concentration difference between strong cations and anions (strong ion difference, or [SID]), causing a metabolic acidosis in peripheral tissues. Central chemoreceptors regulate [Formula: see text] in relation to the [SID] of brain fluids to maintain a "constant" brain [H+]. In addition, increased osmolality, angiotensin II, and vasopressin during exercise may stimulate circumventricular organs of the brain and interact with chemical control of ventilation. Changes in [SID] of brain fluids during exercise are negligible compared to systemic decreases in [SID]; thus, regulation of [Formula: see text] to maintain brain [H+] homeostasis cannot simultaneously compensate for greater changes in [SID] in peripheral tissues. Key words: circumventricular organs, central chemoreception, angiotensin II, vasopressin, alphastat theory

scholarly journals mTORC1 Signaling Contributes to Drinking But Not Blood Pressure Responses to Brain Angiotensin II

Endocrinology ◽  
2016 ◽  
Vol 157 (8) ◽  
pp. 3140-3148 ◽  
Author(s):  
Kenjiro Muta ◽  
Donald A. Morgan ◽  
Justin L. Grobe ◽  
Curt D. Sigmund ◽  
Kamal Rahmouni
Keyword(s):  
Angiotensin Ii ◽  
Water Intake ◽  
Drinking Behavior ◽  
Subfornical Organ ◽  
Dependent Manner ◽  
Ang Ii ◽  
Mtorc1 Signaling ◽  
Wide Range ◽  
The Brain

Mechanistic target of rapamycin complex 1 (mTORC1) is a molecular node that couples extracellular cues to a wide range of cellular events controlling various physiological processes. Here, we identified mTORC1 signaling as a critical mediator of angiotensin II (Ang II) action in the brain. In neuronal GT1–7 cells, we show that Ang II stimulates neuronal mTORC1 signaling in an Ang II type 1 receptor-dependent manner. In mice, a single intracerebroventricular (ICV) injection or chronic sc infusion of Ang II activated mTORC1 signaling in the subfornical organ, a critical brain region in cardiovascular control and fluid balance. Moreover, transgenic sRA mice with brain-specific overproduction of Ang II displayed increased mTORC1 signaling in the subfornical organ. To test the functional role of brain mTORC1 in mediating the action of Ang II, we examined the consequence of mTORC1 inhibition with rapamycin on Ang II-induced increase in water intake and arterial pressure. ICV pretreatment with rapamycin blocked ICV Ang II-mediated increases in the frequency, duration, and amount of water intake but did not interfere with the pressor response evoked by Ang II. In addition, ICV delivery of rapamycin significantly reduced polydipsia, but not hypertension, of sRA mice. These results demonstrate that mTORC1 is a novel downstream pathway of Ang II type 1 receptor signaling in the brain and selectively mediates the effect of Ang II on drinking behavior.

scholarly journals Anatomical Organization of the Rat Subfornical Organ

2021 ◽  
Vol 15 ◽  
Author(s):  
Amirah-Iman Hicks ◽  
Simona Kobrinsky ◽  
Suijian Zhou ◽  
Jieyi Yang ◽  
Masha Prager-Khoutorsky
Keyword(s):  
Angiotensin Ii ◽  
Brain Area ◽  
Third Ventricle ◽  
Circumventricular Organs ◽  
Subfornical Organ ◽  
Histological Techniques ◽  
Neuronal Populations ◽  
Fenestrated Capillaries ◽  
Fenestrated Endothelium ◽  
The Brain

The subfornical organ (SFO) is a sensory circumventricular organ located along the anterodorsal wall of the third ventricle. SFO lacks a complete blood-brain barrier (BBB), and thus peripherally-circulating factors can penetrate the SFO parenchyma. These signals are detected by local neurons providing the brain with information from the periphery to mediate central responses to humoral signals and physiological stressors. Circumventricular organs are characterized by the presence of unique populations of non-neuronal cells, such as tanycytes and fenestrated endothelium. However, how these populations are organized within the SFO is not well understood. In this study, we used histological techniques to analyze the anatomical organization of the rat SFO and examined the distribution of neurons, fenestrated and non-fenestrated vasculature, tanycytes, ependymocytes, glia cells, and pericytes within its confines. Our data show that the shell of SFO contains non-fenestrated vasculature, while fenestrated capillaries are restricted to the medial-posterior core region of the SFO and associated with a higher BBB permeability. In contrast to non-fenestrated vessels, fenestrated capillaries are encased in a scaffold created by pericytes and embedded in a network of tanycytic processes. Analysis of c-Fos expression following systemic injections of angiotensin II or hypertonic NaCl reveals distinct neuronal populations responding to these stimuli. Hypertonic NaCl activates ∼13% of SFO neurons located in the shell. Angiotensin II-sensitive neurons represent ∼35% of SFO neurons and their location varies between sexes. Our study provides a comprehensive description of the organization of diverse cellular elements within the SFO, facilitating future investigations in this important brain area.

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