Subfornical organ: forebrain site of pressor and dipsogenic action of angiotensin II

Intracranial injection of angiotensin II (AII) at three brain sites elicited near simultaneous dipsogenic and pressor effects in rats. Both effects were maximal, occurred with the shortest latencies, and at the lowest doses of AII when the cannula terminated precisely within the parenchyma of the subfornical organ (SFO). Pressor effects were produced by SFO injection of a dose of AII (0.1 pg) which approximates plasma AII concentrations at the high end of the physiological range. Both the drinking and pressor effects were blocked by saralasin. Injections of AII at sites immediately adjacent to SFO produced smaller effects with longer latencies. These results ruled out the possibility that SFO injections were effective via leakage to alternative sites. The pressor effect of AII at the SFO remained in animals under chloralose anesthesia, demonstrating that it is not an artifact of drinking behavior. These results indicate that the SFO is a site of AII pressor action, and confirm previous demonstrations that the structure is a site of AII drinking action.     

Differential neuronal responses to angiotensin III from the subfornical organ of normotensive and spontaneously hypertensive rats

We previously reported that chronic central administration of angiotensin III (AIII) fails to produce sustained drinking behavior in spontaneously hypertensive rats (SHR), possibly because of the development of early desensitization of the angiotensin receptors. The present study extended these findings to the cellular level, using brain-slice preparation from Wistar-Kyoto rats (WKY) and SHR, in conjunction with single-neuron recording in the subfornical organ (SFO), a target site for angiotensin II-induced drinking. We found that a majority of the SFO neurons studied (13/18 in WKY, 20/28 in SHR) responded in a dose-related manner to AIII, given in the range of 10(-6)-10(-5) M. This excitation was receptor-specific, since it was reversed by Ile7-AIII (10(-4)-10(-3) M), the selective AIII antagonist. Bestatin (10(-5)-10(-4) M), an aminopeptidase B inhibitor, did not discernibly affect basal spike frequency when delivered alone. Nevertheless, given in combination with the heptapeptide, bestatin reduced the intensity and duration of SFO neuronal response in WKY to the higher dose (10(-5) M), and in SHR to both doses (10(-6) or 10(-5) M), of AIII. These data suggest that the SFO may also be a central site of action for AIII. Moreover, prolonging the action of AIII by protecting it from being metabolized with bestatin may produce desensitization of the angiotensin receptors on SFO neurons. This was particularly so in the SHR, which are thought to be defective in the degradation of the heptapeptide in the brain.     

Arcuate nucleus inputs onto subfornical organ neurons that respond to plasma hypernatremia and angiotensin II

Experiments were done in urethane anesthetized rats to investigate the effect of electrical and glutamate stimulation of arcuate nucleus (Arc) on the discharge rate of subfornical organ (SFO) neurons that responded to either plasma hypernatremia or angiotensin II (ANG II). Extracellular recordings were made from 253 histologically verified single neurons in SFO. Of these, 40.3% (102/253) responded with excitation and 10% (25/253) with inhibition to Arc stimulation. Thirty-five (34.3%) of the units excited by Arc were also excited by intracarotid infusion of hypertonic (0.5 M) NaCl. In addition, 37 (36.3%) of the units excited by Arc were also excited by intracarotid infusion of ANG II. Furthermore, 10 (40.0%) of the units inhibited by Arc were found to be excited by ANG II. None of the units inhibited by Arc stimulation were responsive to plasma hypernatremia. These data indicate that inputs from Arc neurons converge onto SFO neurons that alter their discharge rate during changes in plasma concentration of Na+ or ANG II. These results suggest that Arc may be involved in body fluid balance and circulatory regulation by modulating the activity of SFO neurons that function in the detection of blood-borne signals from the depletion of intra- and extra-cellular fluid volumes.     

Impaired drinking responses of rats with lesions of the subfornical organ.

Electrolytic lesions of the subfornical organ (SFO) in rats are known to abolish their drinking response to iv infusion of angiotensin II (AII). Such lesions also attenuate drinking after 20% polyethylene glycol solution (PEG) is given sc, which suggests that AII may play an important role in mediating thirst during hypovolemia. However, the 3 present studies show that male albino Sprague-Dawley rats (N?=?57) with SFO lesions drank normal amounts when larger plasma volume deficits were caused by 30% PEG treatment. Ss did not drink in response to relatively low doses of hypertonic saline but drank normal amounts when given larger doses. Results suggest that the SFO is involved in a control system for thirst and that after damage to it, greater stimulation than usual may be required for drinking to be initiated. From this perspective, drinking would be expected following either suprathreshold stimulation or drug-induced lowering of the activation threshold in these animals, as was observed, with the loss of putative AII receptors in the SFO also contributing to their particularly severe deficits in thirst induced by AII. (37 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Peptide and acetylcholine action on neurones of the cat subfornical organ

This paper presents evidence for an IgG1 allotype detected by a sheep antibovine serum. The character which appears to be inherited in a simple Mendelian way has been named G1a1.     

Effect of glutamate and angiotensin II on whole cell currents and release of nitric oxide in the rat subfornical organ

Blood-borne angiotensin II (AngII) is known to mediate water-intake by its excitatory effect on neurons in the subfornical organ (SFO). Conversely, nitric oxide (NO) has exclusively inhibitory effects on rat SFO-neurons and on SFO-mediated water-intake. Extracellular and patch-clamp recordings from freshly dissociated rat SFO-neurons showed that glutamate activates AngII-sensitive SFO-neurons by opening ligand-gated cation channels. An immunocytochemical study showed that activation of glutamate receptors increased the concentration of the inhibitory second messenger cGMP in the SFO. A model is proposed suggesting that NO protects SFO-neurons from overexcitability by excitatory neurotransmitters.     

Atrial natriuretic peptide in the subfornical organ reduces drinking induced by angiotensin or in response to water deprivation.

Three experiments tested whether the subfornical organ (SFO) could be a site of action for the antidipsogenic effects of atrial natriuretic peptide (ANP) in rats. Pretreatment with 100, 230, or 500 pmol ANP in the SFO reduced drinking induced by 10 pmol angiotensin II in the SFO. Drinking in response to water deprivation was reduced by ANP in rats having cannulas in or near the SFO, but not in rats having cannulas distant from the SFO or in the ventricles. Finally, ANP had no effect on eating or drinking after food deprivation, suggesting that the rats in the other experiments were not acutely incapacitated. The SFO may mediate the central effects of ANP on drinking induced by angiotensin or in response to water deprivation and could play a similar role in the central effects of ANP on salt appetite, diuresis, vasopressin secretion, and blood pressure. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Drinking and Fos-immunoreactivity in rat brain induced by local injection of angiotensin I into the subfornical organ

Previous studies suggested that angiotensinergic stimulation in the subfornical organ (SFO) has effects on the anterior third ventricle (AV3V) region and the hypothalamus for dipsogenic response and vasopressin release. In this study, Angiotensin I (ANG I) was directly injected into the SFO and this stimulated drinking. Injection of ANG I into the SFO also induced Fos-immunoreactivity (Fos-ir) in the AV3V region and in the vasopressin neurons of the supraoptic and paraventricular nuclei (SON and PVN). Pretreatment of the SFO with either captopril, an ANG converting enzyme inhibitor, or losartan, an AT1 receptor antagonist, abolished both drinking and Fos-ir induced by ANG I. Water intake partially decreased ANG I-induced Fos-ir in the SON and PVN, but not in the other areas. These results indicate that there is an ANG converting system in the SFO and suggest that neurons in the AV3V region and vasopressin cells in the hypothalamus can be regulated by angiotensinergic components in the SFO.     

Angiotensin-converting enzyme in subfornical organ mediates captopril-induced drinking.

These experiments tested whether angiotensin-converting enzyme (ACE) located within the subfornical organ (SFO) participates in the generation of water intake during peripheral ACE blockade with captopril (CAP). Lesions of the SFO virtually abolished drinking in response to intraperitoneal CAP injection. Intracranially injected CAP suppressed drinking induced by intraperitoneal CAP more completely with direct SFO injection compared with intraventricular or control tissue injections. This central captopril treatment did not alter the drinking response to subcutaneous hypertonic saline. Intraventricular injections of the angiotensin II (ANG II) receptor blocker sarile reduced drinking during oral captopril treatment in rats rehydrating from water deprivation. The results indicate that (a) the SFO mediates drinking caused by peripheral ACE inhibition; (b) the ACE located within the SFO may locally convert ANG I to ANG II, which then stimulates thirst; and (c) central ANG II receptors mediate thirst caused by peripheral ACE inhibition. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of angiotensin II and its blockers Sar1-Ile8-angiotensin II and DuP 753 on drinking in ducks in relation to properties of subfornical organ neurons

Properties of systemically applied angiotensin II in stimulating water intake of normally hydrated ducks were studied and the results compared with properties of angiotensin II-responsive neurons of the subfornical organ which are considered as targets for circulating angiotensin II acting as a dipsogen. Following intravenous infusion of hypertonic saline (2000 mosmol.kg-1 at 0.3 ml.min-1 for 1 h), intravenous infusion of 0.3 ml.min-1 isotonic saline with angiotensin II (200 ng.min-1), starting 1 h later, stimulated drinking in each case at an angiotensin II plasma level of about 1400 pg.ml-1. Without hypertonic priming, the same angiotensin II infusion did not stimulate drinking in each experiment; however, if effective, repeated infusions of ANGII induced stable dipsogenic responses. Angiotensin II infusions did not alter plasma levels of antidiuretic hormone. Sar1-Ile8-angiotensin II, a non-selective angiotensin II antagonist, acted weakly as a partial agonist when infused at a dose 200-fold higher than angiotensin II and effectively blocked the dipsogenic action of angiotensin II; this corresponds to the inhibition of angiotensin II-induced excitation by Sar1-Ile8-angiotensin II observed in duck subfornical organ neurons. DuP 753 (losartan), an angiotensin II antagonist specifically blocking AT1 receptors in mammals, had equivocal effects on angiotensin II-induced drinking in ducks at rates 50- and 200-fold higher than angiotensin II, which corresponds to the weak inhibitory action of this compound on angiotensin II-induced neuronal excitation in the duck SFO. Blood pressure was only marginally elevated by the applied angiotensin II dose and Sar1-Ile8-angiotensin II had no effect.     

Localization of angiotensin AT1 receptors in the rat heart conduction system

We characterized angiotensin II receptor subtypes in the conduction system of the rat heart using quantitative autoradiography. In both the sinoatrial and atrioventricular nodes, binding could be totally displaced by losartan, and was insensitive to PD 123177, indicating that angiotensin II receptors in the conduction system of the rat heart belong to the AT1 subtype. Angiotensin AT1 receptors could play a direct role in the regulation of the heart chronotropic properties.     

Regional differences in the morphology of the rat subfornical organ

Properties of whole milk and milk fractions from cows fed a diet that gave a greatly increased proportion of unsaturated fatty acid residues (especially of linoleic acid) in the milk lipids were studied, and this milk (high-linoleic milk) was compared with milk from cows on a control diet (control milk). The milk fractions were isolated by high-speed centrifugation of whole milk or cream and were examined by chemical analysis and electron microscopy. During centrifugation the globules of milk fat were disrupted and the membranes (fat-globule 'ghosts') floated as a layer beneath the free lipid. Membrane proteins from the 2 sorts of milk gave the same electrophoretic pattern and the amino acid compositions were the same. Lipid analysis of the membrane fraction from high-linoleic milk showed the expected increase in the proportion of unsaturated fatty acid residues in the neutral lipids, but there was an unexpected decrease in the proportion of unsaturated residues in the membrane phospholipids. No differences were found between high-linoleic and control milk in the ultrastructure of the milk-fat globules or the isolated membranes.     

The hyperglycemia induced by angiotensin II in rats is mediated by AT1 receptors

We have shown that the renin-angiotensin system (RAS) is involved in glucose homeostasis during acute hemorrhage. Since almost all of the physiological actions described for angiotensin II were mediated by AT1 receptors, the present experiments were designed to determine the participation of AT1 receptors in the hyperglycemic action of angiotensin II in freely moving rats. The animals were divided into two experimental groups: 1) animals submitted to intravenous administration of angiotensin II (0.96 nmol/100 g body weight) which caused a rapid increase in plasma glucose reaching the highest values at 5 min after the injection (33% of the initial values, P < 0.01), and 2) animals submitted to intravenous administration of DuP-753 (losartan), a non-peptide antagonist of angiotensin II with AT1-receptor type specificity (1.63 mumol/100 g body weight as a bolus, i.v., plus a 30-min infusion of 0.018 mumol 100 g body weight-1 min-1 before the injection of angiotensin II), which completely blocked the hyperglycemic response to angiotensin II (P < 0.01). This inhibitory effect on glycemia was already demonstrable 5 min (8.9 +/- 0.28 mM, angiotensin II, N = 9 vs 6.4 +/- 0.22 mM, losartan plus angiotensin II, N = 11) after angiotensin II injection and persisted throughout the 30-min experiment. Controls were treated with the same volume of saline solution (0.15 M NaCl). These data demonstrate that the angiotensin II receptors involved in the direct and indirect hyperglycemic actions of angiotensin II are mainly of the AT1-type.     

Type 1 angiotensin II receptors in human endometrium

OBJECTIVE: This paper is the summary of "National Symposium on the Value of Immunodiagnostic Assays in Schistosomiasis by Treatment Effects Assessment" which was directed by the Expert Advisory Committee for Schistosomiasis of the Ministry of Public Health. This symposium was held to evaluate the diagnostic effects of the new system of detection in the sensitivity and specificity by treatment assessment. MATERIALS AND METHODS: Twelve laboratories with 14 assay systems participated in this collaborative study, in which, 450 sera were detected by double blind trial using a classical antibody detection with ELISA as a control. RESULTS: The results showed that 6 test systems were superior or close to the classical antibody detection, especially in evaluating the value of treatment effects. CONCLUSIONS: It is unanimously recognized that much progress has been made in the research of immunodiagnosis of schistosomiasis in China, but many problems remain to be solved and worth further studying.     

Effects of subfornical organ extracts of salt-water balance in the rat

The subfornical organ (SFO) is regarded as a neurosecretory structure but no information is available on the nature or biological effects of the secretory products(s). Supernatants of water homogenates of rat SFO were lyophilized and reconsittuted in artificial cerebrospinal fluid (CSF). Intracerebroventricular (IVT), but not subcutaneous, administration of this material to rats produced diuresis, natriuresis and kaliuresis in the following 8 h daylight period. During the overnight cycle, consummatory behavior and excretion of sodium and potassium were reduced. Similar responses were obtained after IVT administration of cerebellar cortex (CB) or large amounts of plasma. SFO, CB and cerebral cortex (CC) were incubated in potassium-enriched CSF to enhance release of secretory products. Urine volume was increased 8 h after IVT injection of SFO media; in the overnight cycle, food consumption, absolute urinary sodium and potassium, and [Na+-a1 were reduced. These effects were not produced by IVT injection of CC or CB media, or equal amounts of plasma proteins. Additional experiments demonstrated that choroid plexi and SFO effects were similar and that the active SFO material was dialyzable and thermal stable. These data suggest that SFO contains a water-soluble substance which is released into a posassium-enriched medium. The material is heat stable, has a relatively low molecular weight, and alters salt-water balance after injection into ventricular cerebrospinal fluid.     

Interaction of hydration and subfornical organ lesions in sodium-depletion induced salt appetite.

The authors tested whether the level of hydration after furosemide diuresis and 22 hrs of sodium depletion affects the amount of water or 0.3 M NaCl solution consumed by rats with intact brains or with lesions of the subfornical organ (SFO). Rats received 2 (underhydrated) or 10 (euhydrated) ml/kg water by gavage as the only fluid input 2, 4, and 20 hrs after 10 mg/kg furosemide. These hydration treatments had little or no effect on the amount of saline consumed in 2 hrs by intact rats. SFO lesions reduced water intake regardless of hydration condition. Euhydrated, SFO-lesioned rats drank a normal amount of saline, but underhydrated, lesioned rats drank less saline than any other group. Thus, euhydration may facilitate salt appetite in SFO-lesioned rats, and the deficits in salt appetite noted in SFO-lesioned rats may result from deficits in water ingestion rather than from a destruction of angiotensin II receptor sites that directly provoke salt appetite. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Long duration pressor responses following activation of subfornical organ neurons in rats are the result of increased circulating vasopressin

Electrical stimulation in the subfornical organ (SFO) of male Sprague-Dawley rats resulted in biphasic increases in blood pressure (BP) without a change in heart rate. The initial short duration (0-10 s) increase in BP lasted throughout the 10 s stimulation period (area under the curve (AUC) = 104.3+/-15.26 mmHg/s, (mean+/-SEM) P < 0.001). Upon termination of the electrical stimulus, the BP remained elevated for approximately 55 s (long duration response, AUC = 327.5+/-48.22 mmHg/s, P < 0.001). This long duration BP response was determined to be the result of an increase in circulating vasopressin (VP) as administration of a V1 receptor antagonist abolished this response (AUC = -210.7 +/- 42.38 mmHg/s, P < 0.01). The results of the present study demonstrate that the long duration component of the biphasic increase in BP observed on response to electrical stimulation of the SFO is the result of increased concentrations of circulating VP.     

Dependence of adrenalectomy-induced sodium appetite on the action of angiotensin II in the brain of the rat.

Adrenalectomized rats express a robust sodium appetite that is accompanied by high levels of blood-borne angiotensin II and is caused by angiotensin II of cerebral origin. Blood-borne angiotensin II is elevated in rats consuming NaCl after adrenalectomy, and plasma angiotensin II concentrations are increased further when the animals cannot drink a NaCl solution. These phenomena are the result of the pathological removal of aldosterone, because replacement therapy returned both sodium intake and plasma angiotensin II concentrations to preadrenalectomy levels. The adrenalectomized rat's appetite for sodium is completely suppressed by interference with the central, but not the peripheral, action of angiotensin II. These data demonstrate that the mechanism of the sodium appetite of the adrenalectomized rat is a pathological instance of the angiotensin/aldosterone synergy that governs the sodium appetite of the adrenal-intact, sodium-depleted rat. Because aldosterone has been removed, angiotensin acts alone to produce the appetite. Furthermore, the data show that it is angiotensin II of central origin that is important for sodium appetite expression. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Induction of angiotensin converting enzyme and angiotensin II receptors in the atherosclerotic aorta of high-cholesterol fed Cynomolgus monkeys

Psychometric characteristics of the Social Introversion (Si) scale, the Social Discomfort (SOD) scale, and the Si subscales of the MMPI-2 were examined in clinical samples of 122 psychiatric patients and 399 patients with substance-use disorders. The combined Si1 (Shyness/Self-Consciousness) and Si2 (Social Avoidance) subscales correlated highly with SOD and are apparent measures of the social introversion construct. Si3 (Self/Other Alienation) was found to be a measure of the general maladjustment factor of the MMPI-2. Content not included on the Si subscales was divided into a group of items that measures general maladjustment and 2 other item groups that may assess minor constructs related to social introversion. As in previous research, the 3 Si subscales accounted well for variance in Si scores.