Search

Multiple neurological problems have been reported in coronavirus disease-2019 (COVID-19) patients because severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) likely spreads to the central nervous system (CNS) via olfactory nerves or through the subarachnoid space along olfactory nerves into the brain's cerebrospinal fluid and then into the brain's interstitial space. We hypothesize that SARS-CoV-2 enters the subfornical organ (SFO) through the above routes and the circulating blood since circumventricular organs (CVOs) such as the SFO lack the blood-brain barrier, and infection of the SFO causes dysfunction of the hypothalamic paraventricular nucleus (PVN) and supraoptic nucleus (SON), leading to hydroelectrolytic disorder. SARS-CoV-2 can readily enter SFO-PVN-SON neurons because these neurons express angiotensin-converting enzyme-2 receptors and proteolytic viral activators, which likely leads to neurodegeneration or neuroinflammation in these regions. Considering the pivotal role of SFO-PVN-SON circuitry in modulating hydroelectrolyte balance, SARS-CoV-2 infection in these regions could disrupt the neuroendocrine control of hydromineral homeostasis. This review proposes mechanisms by which SARS-CoV-2 infection of the SFO-PVN-SON pathway leads to hydroelectrolytic disorder in COVID-19 patients., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

The vascular organ of the lamina terminalis, subfornical organ (SFO), and area postrema comprise the sensory circumventricular organs (CVO) which are central structures that lie outside the blood brain barrier and are thought to provide an interface between peripherally circulating signals and the brain through their projections to central autonomic structures. The SFO expresses mRNA for the G protein-coupled apelin receptor (APJ, gene name aplnr) and exogenous microinjection of the neuropeptide apelin (apln) to the SFO elicits a depressor effect. Here we investigated the expression and cellular distribution of aplnr, apln and the recently described ligand apela (apela) in the CVOs and investigated whether differences in the levels of expression of apelinergic gene transcripts in these regions might underlie the chronic elevated blood pressure seen in hypertension. We carried out multiplex in situ hybridization histochemistry on CVO tissue sections from spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto (WKY) controls. Confocal immunofluorescent images indicated strong aplnr expression, with lower levels of apln and modest apela expression, in the CVOs of both WKY rats and SHRs, in both neurons and glia. The expression level of aplnr transcripts was increased in the SFO of SHRs compared to WKY rats. Our data may highlight a potential dysfunction in the communication between CVOs and downstream signalling pathways in SHRs, which may contribute to its different phenotype/s., Competing Interests: The authors have declared that no competing interests exist.

Adipsic (or essential) hypernatremia is a rare hypernatremia caused by a deficiency in thirst regulation and vasopressin release. In 2010, we reported a case in which autoantibodies targeting the sensory circumventricular organs (sCVOs) caused adipsic hypernatremia without hypothalamic structural lesions demonstrable by magnetic resonance imaging (MRI); sCVOs include the subfornical organ (SFO) and organum vasculosum of the lamina terminalis (OVLT), which are centers for the monitoring of body-fluid conditions and the control of water and salt intakes, and harbor neurons innervating hypothalamic nuclei for vasopressin release. We herein report three newly identified patients (3- to 8-year-old girls on the first visit) with similar symptoms. The common features of the patients were extensive hypernatremia without any sensation of thirst and defects in vasopressin response to serum hypertonicity. Despite these features, we could not detect any hypothalamic structural lesions by MRI. Immunohistochemical analyses using the sera of the three patients revealed that antibodies specifically reactive to the mouse SFO were present in the sera of all cases; in one case, the antibodies also reacted with the mouse OVLT. The immunoglobulin (Ig) fraction of serum obtained from one patient was intravenously injected into wild-type mice to determine whether the mice developed similar symptoms. Mice injected with a patient's Ig showed abnormalities in water/salt intake, vasopressin release, and diuresis, which resultantly developed hypernatremia. Prominent cell death and infiltration of reactive microglia was observed in the SFO of these mice. Thus, autoimmune destruction of the SFO may be the cause of the adipsic hypernatremia. This study provides a possible explanation for the pathogenesis of adipsic hypernatremia without demonstrable hypothalamus-pituitary lesions., (© 2016 International Society of Neuropathology.)

Angiotensin II (AngII) elicits the production of superoxide (O 2 •- ) from mitochondria in numerous cell types within peripheral organs and in the brain suggesting a role for mitochondrial-produced O 2 •- in the pathogenesis of hypertension. However, it remains unclear if mitochondrial O 2 •- is causal in the development of AngII-induced hypertension, or if mitochondrial O 2 •- in the absence of elevated AngII is sufficient to increase blood pressure. Further, the tissue specific (i.e. central versus peripheral) redox regulation of AngII hypertension remains elusive. Herein, we hypothesized that increased mitochondrial O 2 •- in the absence of pro-hypertensive stimuli, such as AngII, elevates baseline systemic mean arterial pressure (MAP), and that AngII-mediated hypertension is exacerbated in animals with increased mitochondrial O 2 •- levels. To address this hypothesis, we generated novel inducible knock-down mouse models of manganese superoxide dismutase (MnSOD), the O 2 •- scavenging antioxidant enzyme specifically localized to mitochondria, targeted to either the brain subfornical organ (SFO) or peripheral tissues. Contrary to our hypothesis, knock-down of MnSOD either in the SFO or in peripheral tissues was not sufficient to alter baseline systemic MAP. Interestingly, when mice were challenged with chronic, peripheral infusion of AngII, only the MnSOD knock-down confined to the SFO, and not the periphery, demonstrated an increased sensitization and potentiated hypertension. In complementary experiments, over-expressing MnSOD in the SFO significantly decreased blood pressure in response to chronic AngII. Overall, these studies indicate that mitochondrial O 2 •- in the brain SFO works in concert with other AngII-dependent factors to drive an increase in MAP, as elevated mitochondrial O 2 •- alone, either in the SFO or peripheral tissues, failed to raise baseline blood pressure., (Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.)

Water deprivation (WD) induces changes in plasma volume and osmolality, which in turn activate several responses, including thirst, the activation of the renin-angiotensin system (RAS) and vasopressin (AVP) and oxytocin (OT) secretion. These systems seem to be influenced by oestradiol, as evidenced by the expression of its receptor in brain areas that control fluid balance. Thus, we investigated the effects of oestradiol treatment on behavioural and neuroendocrine changes of ovariectomized rats in response to WD. We observed that in response to WD, oestradiol treatment attenuated water intake, plasma osmolality and haematocrit but did not change urinary volume or osmolality. Moreover, oestradiol potentiated WD-induced AVP secretion, but did not alter the plasma OT or angiotensin II (Ang II) concentrations. Immunohistochemical data showed that oestradiol potentiated vasopressinergic neuronal activation in the lateral magnocellular PVN (PaLM) and supraoptic (SON) nuclei but did not induce further changes in Fos expression in the median preoptic nucleus (MnPO) or subfornical organ (SFO) or in oxytocinergic neuronal activation in the SON and PVN of WD rats. Regarding mRNA expression, oestradiol increased OT mRNA expression in the SON and PVN under basal conditions and after WD, but did not induce additional changes in the mRNA expression for AVP in the SON or PVN. It also did not affect the mRNA expression of RAS components in the PVN. In conclusion, our results show that oestradiol acts mainly on the vasopressinergic system in response to WD, potentiating vasopressinergic neuronal activation and AVP secretion without altering AVP mRNA expression., (© 2016 Society for Endocrinology.)

The subfornical organ (SFO) has highly permeable fenestrated vasculature and is a key site for immune-to-brain communications. Recently, we showed the occurrence of continuous angiogenesis in the SFO. In the present study, we found that systemic administration of bacterial lipopolysaccharide (LPS) reduced the vascular permeability and endothelial cell proliferation. In LPS-administered mice, the SFO vasculature showed a significant decrease in the immunoreactivity of plasmalemma vesicle associated protein-1, a marker of endothelial fenestral diaphragms. These data suggest that vasculature undergoes structural change to decrease vascular permeability in response to systemic LPS administration., (Copyright © 2016. Published by Elsevier B.V.)

Our previous work indicated that the subfornical organ (SFO) is an important brain sensor of blood-borne proinflammatory cytokines, mediating their central effects on autonomic and cardiovascular function. However, the mechanisms by which SFO mediates the central effects of circulating proinflammatory cytokines remain unclear. We hypothesized that proinflammatory cytokines act within the SFO to upregulate the expression of excitatory and inflammatory mediators that drive sympathetic nerve activity. In urethane-anesthetized Sprague-Dawley rats, direct microinjection of tumor necrosis factor (TNF)-α (25 ng) or interleukin (IL)-1β (25 ng) into SFO increased mean blood pressure, heart rate, and renal sympathetic nerve activity within 15 to 20 minutes, mimicking the response to systemically administered proinflammatory cytokines. Pretreatment of SFO with microinjections of the angiotensin II type-1 receptor blocker losartan (1 μg), angiotensin-converting enzyme inhibitor captopril (1 μg) or cyclooxygenase-2 inhibitor NS-398 (2 μg) attenuated those responses. Four hours after the SFO microinjection of TNF-α (25 ng) or IL-1β (25 ng), mRNA for angiotensin-converting enzyme, angiotensin II type-1 receptor, TNF-α and the p55 TNF-α receptor, IL-1β and the IL-1R receptor, and cyclooxygenase-2 had increased in SFO, and mRNA for angiotensin-converting enzyme, angiotensin II type-1 receptor, and cyclooxygenase-2 had increased downstream in the hypothalamic paraventricular nucleus. Confocal immunofluorescent images revealed that immunoreactivity for the p55 TNF-α receptor and the IL-1 receptor accessory protein, a subunit of the IL-1 receptor, colocalized with angiotensin-converting enzyme, angiotensin II type-1 receptor-like, cyclooxygenase-2, and prostaglandin E2 EP3 receptor immunoreactivity in SFO neurons. These data suggest that proinflammatory cytokines act within the SFO to upregulate the expression of inflammatory and excitatory mediators that drive sympathetic excitation., (© 2015 American Heart Association, Inc.)

Many investigations have been devoted to determining the role of angiotensin II (ANG II) and aldosterone (ALD) in sodium-depletion-induced sodium appetite, but few were focused on the mechanisms mediating the salty taste changes accompanied with sodium depletion. To further elucidate the mechanism of renin-angiotensin-aldosterone system (RAAS) action in mediating sodium intake behavior and accompanied salty taste changes, the present study examined the salty taste function changes accompanied with sodium depletion induced by furosemide (Furo) combined with different doses of angiotensin converting enzyme (ACE) inhibitor, captopril (Cap). Both the peripheral and central RAAS activity and the nuclei Fos immunoreactivity (Fos-ir) expression in the forebrain area were investigated. Results showed that sodium depletion induced by Furo+low-Cap increased taste preference for hypertonic NaCl solution with amplified brain action of ANG II but without peripheral action, while Furosemide combined with a high dose of captopril can partially inhibit the formation of brain ANG II, with parallel decreased effects on salty taste changes. And the resulting elevating forebrain ANG II may activate a variety of brain areas including SFO, PVN, SON and OVLT in sodium depleted rats injected with Furo+low-Cap, which underlines salty taste function and sodium intake behavioral changes. Neurons in SFO and OVLT may be activated mainly by brain ANG II, while PVN and SON activation may not be completely ANG II dependent. These findings suggested that forebrain derived ANG II may play a critical role in the salty taste function changes accompanied with acute sodium depletion., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Although endoplasmic reticulum (ER) stress is a pathologic mechanism in a variety of chronic diseases, it is unclear what role it plays in chronic hypertension (HTN). Dysregulation of brain mechanisms controlling arterial pressure is strongly implicated in HTN, particularly in models involving angiotensin II (Ang II). We tested the hypothesis that ER stress in the brain is causally linked to Ang II-dependent HTN. Chronic systemic infusion of low-dose Ang II in C57BL/6 mice induced slowly developing HTN, which was abolished by co-infusion of the ER stress inhibitor tauroursodeoxycholic acid (TUDCA) into the lateral cerebroventricle. Investigations of the brain regions involved revealed robust increases in ER stress biomarkers and profound ER morphological abnormalities in the circumventricular subfornical organ (SFO), a region outside the blood-brain barrier and replete with Ang II receptors. Ang II-induced HTN could be prevented in this model by selective genetic supplementation of the ER chaperone 78-kDa glucose-regulated protein (GRP78) in the SFO. These data demonstrate that Ang II-dependent HTN is mediated by ER stress in the brain, particularly the SFO. To our knowledge, this is the first report that ER stress, notably brain ER stress, plays a key role in chronic HTN. Taken together, these findings may have broad implications for the pathophysiology of this disease.

Accumulating evidence suggests that structures within the lamina terminalis; the organum vasculosm of the lamina terminalis (OVLT), the median preoptic nucleus (MnPO) and/or the subfornical organ (SFO); are required for the development of DOCA-salt hypertension. Lesion of the anteroventral tissue lining the third ventricle (AV3V), which destroys cell bodies in the OVLT and MnPO, as well as efferent projections from the SFO to the OVLT and MnPO, abolishes DOCA-salt hypertension in the rat. However, the individual contribution of these structures to DOCA-salt hypertension is unknown. The present study was designed to determine whether an intact SFO is required for hypertension development in the DOCA-salt model. In uninephrectomized SFO lesioned (SFOx; n=6) and SHAM (n=8) Sprague-Dawley rats, 24-h mean arterial pressure (MAP) and heart rate (HR) were continuously recorded telemetrically 4 days before and 36 days after DOCA implantation (100 mg/rat; s.c.); 24-h sodium and water balances were measured throughout the protocol. No differences in control MAP, HR, sodium and water balances were observed between groups. Following DOCA implantation, the magnitude of the elevation of MAP was similar between groups (approximately 40 mm Hg) so that by Day 40, MAP was 148+/-5 mm Hg in SFOx and 145+/-4 mm Hg in SHAM rats. The magnitude of decrease in HR from control values was similar in both groups. Differences in sodium and water balances were not observed between groups. We conclude that the SFO alone does not play a significant role in the development of mineralocorticoid-salt hypertension.

Objectives: Circumventricular organs (CVOs) are fine, periventricular, neurotransmitter-rich structures that are devoid of a blood-brain barrier and are known for their secretory role controlling fluid and electrolyte balance, thirst and even reproduction. Common pathologies of the brain such as trauma or bleeding affect CVOs, and hence their function. However, at what stage of these disease processes are CVOs affected and the time sequence of their recovery is still not clear. The aim of this study was to detect the morphological changes in CVOs using electron microscopy after experimental subarachnoid hemorrhage (SAH)., Methods: Experimental SAH was induced by transclival puncture of the basilar artery. Both scanning and transmission electron microscopic examination of the representive sections from each CVO was undertaken., Results: Electron microscopy has shown that after SAH, the cells that form the CVOs exhibit signs of cellular necrosis with margination of the nucleus as well as cytoplasmic, mitochondrial and axonal edema. The subfornicial organ and organum vasculosum lamina terminalis appear to be more vulnerable to the effects of SAH than the median eminence or area postrema., Discussion: Considering the fact that the experimental SAH model we have used is very similar to the momentary rupture of an aneurysm with secondary reflex spasm to seal the hole, it will not be unrealistic to consider that similar effects may also take place in the clinical setting.

In order to investigate the role of heme oxygenase-1 (HO-1) in the molecular mechanism of experimental allergic encephalomyelitis (EAE), which was induced by guinea pig spinal cord homogenate + complete freund adjuvant on Wistar rats, we observed the gene of HO-1 and its protein expression with reverse transcriptase polymerase chain reaction(RT-PCR) and immunohistochemistry 1, 7, 14, and 21 d after EAE induction in rats. The relationship between HO-1 and the symptoms of EAE was also observed. The results showed that the levels of HO-1 mRNA and its protein expression were very low in the brains of the control group, whereas they were enhanced gradually with pathological course in the brain and onsets of symptoms, signs of EAE. On day 7, the level of HO-1 mRNA reached the peak, but the expression level of HO-1 protein in the brains reached the peak on day 14. The immunoreactive cells of HO-1 were mainly located at the choroid plexuses and subfornical organ (SFO), as well as in regions around the "sleeve-like" lesion foci, all of which were coincident with the locations of lesions of EAE. The levels of HO-1 mRNA and its protein expression were lowered gradually on day 21, which were in parallel with the severities of symptoms and signs of EAE. After a specific inhibitor of HO-1, Snpp-9, was applied, both of the symptoms and pathological lesions of EAE in the rat brains were mitigated markedly. Therefore, these results may suggest that the dynamic changes of HO-1 mRNA and its protein expression are in parallel with the changes of symptoms and pathological lesions of EAE in the brain. In conclusion, the levels of HO-1 mRNA and its protein expression in brains may play an important role in the pathogenesis of EAE, and application of inhibitors of HO-1 may be one of the potential therapeutic ways for the prevention and treatment of EAE.

The parenteral administration of monosodium glutamate (MSG) to neonatal rats induces specific lesions in the central nervous system that lead to a well characterized neuroendocrinological dysfunction. Additionally, it has been shown that MSG-treated rats present a blunted blood pressure response to the injection of nitric oxide synthase inhibitors. Recently, a similar cardiovascular alteration has been reported after the electrolytic lesion of the anteroventral region of the third ventricle affecting the connections of the subfornical organ (SFO). We hypothesized that the treatment of neonatal rats with MSG could affect the nitrergic cells of the SFO. In the present work, we have looked for alterations in the NADPH-diaphorase activity (a commonly used marker for nitrergic neurons) in the SFO of MSG-treated rats of either sex and at two different ages. Our results shown that the treatment of neonatal rats with MSG induced a substantial reduction in the volume of the SFO and in the number of its nitrergic cells with regard to control animals. These findings suggest that the SFO could be implicated in some of the cardiovascular alterations observed in MSG-treated rats.

Nests of cells within the central nervous system, namely the circumventricular organs (CVOs) which include the subfornical organ (SFO), organum vasculosum lamina terminalis (OVLT), area postrema (AP) and the median eminence (ME) are known to contain not only receptors for angiotensin II (ANG II) but also ANG II itself. Though the significance of this central ANG II network in the pathophysiology of certain conditions like hypertension is well established, there appears to be a lack of knowledge as to how this system might be involved after subarachnoid haemorrhage (SAH). In this study, we have investigated ANG II receptor content change at various circumventricular organs after experimental subarachnoid haemorrhage in rats using a transcervical transclival model. ANG II receptor content was detected by in vivo autoradiography using intracisternal ANG II Sar 1, Ile 8 labelled with iodine (I) 125 both at 30 minutes and 48 hours after the SAH. Serum angiotensin converting enzyme activity was also detected during the time course reflecting the involvement of the peripheral angiotensin system and showed an early rise and a fall after two days. Immunohistochemistry was utilized to show the ANG II-containing cells within the circumventricular organs. SFO and OVLT were found to have a statistically significant increase in ANG II receptor content persisting over two days after the SAH. These alterations in the receptor content of CVOs may indicate their possible role in delayed ischaemic deficits seen after SAH.

The activity of subfornical organ (SFO) neurons that were antidromically identified by electrical stimulation of the rat hypothalamic paraventricular nucleus (PVN) was tested for a response to microiontophoretic application of angiotensin II (ANG II) or hemorrhage (10 ml/kg b.w.t.). Microiontophoretically (MIPh) applied ANG II caused an increased excitability in 24 out of 28 neurons tested and the excitation was blocked by MIPh-applied saralasin (Sar), a specific ANG II antagonist. Of these neurons that responded to ANG II, 14 displayed an increase in neuronal firing in response to hemorrhage, while 10 were unresponsive. The excitatory response to hemorrhage in 5 out of 14 neurons tested was prevented by MIPh-applied Sar, whereas the response of the remaining neurons was not affected. These results show that part of SFO neurons projecting to the PVN may receive neural inputs from the peripheral baroreceptors, and suggest that the inputs may be partially attributable to the involvement of central angiotensinergic circuits.

We have studied the development of the nuclear sizes of ependymocytes and neurons of two circumventricular organs of the male alcoholic mouse: the Subfornical Organ (SFO) and the Area Postrema (AP), comparing the results with a control group. The global volume of both centers was also studied. The results show that the SFO, a structure related to the control of fluid balance, responds to alcoholism with an increase of the global volume. This increase could be related to the variations of salt-water balance and/or blood pressure in chronic alcoholism. However, the size of cell nuclei in the SFO is not affected. In contrast, the AP responds to chronic alcoholism like other nervous centres, with a decrease of the nuclear size of its cells. The global volume of AP does not change.

Mice were treated with ethanol vapour for 6 weeks and the circumventricular area of the brains prepared for light and electron microscopy. No abnormalities were found in the subfornical organ, but degeneration was found in the medial preoptic area in 2 of the 6 ethanol-treated animals. There was no indication of functional impairment of brain or body water regulation mechanisms.

Several experiments tested whether the subfornical organ (SFO) is necessary for water or NaCl intake arising from angiotensin-converting enzyme (CE) blockade with captopril (CAP) in the drinking fluids (0.1 mg/ml). Peripheral CAP was given to rats acutely following 24-h water deprivation or chronically over several days, either with water alone available for drinking or with 0.3 M NaCl in choice with water. Control rats drank more water, and NaCl when it was available, during CAP treatment, whereas rats with SFO damage increased NaCl intake only. CAP decreased urinary volume (UV) and increased urinary potassium excretion (UKV) during rehydration with only water available and increased urinary sodium excretion (UNaV) with NaCl present. Regardless of CAP treatment, rats with SFO damage had increased electrolyte concentrations and excretions during rehydration with only water available and increased UK with NaCl present, compared with controls. Oral CAP did not have an aversive taste at the dose used here. We conclude that the SFO is necessary for CAP-enhanced water, but not NaCl, intake and suggest that different neurological mechanisms control ingestion of each fluid during CAP.

The authors investigated characteristics of the rat subfornical organ as chronically affected by increased ambient temperature and under the conditions of intermittent hypoxic hypothermia. The histological and stereological parameters analysed point to a stimulated functioning of the rat subfornical organ under temperature stress.

We have examined the effects of systemic angiotensin II (AII) on plasma oxytocin (OXY) concentrations in freely moving male Sprague-Dawley rats. We have also examined the role of the subfornical organ (SFO) as a CNS site at which circulating AII acts to influence secretion of this neurohypophysial peptide. OXY concentrations were measured by radioimmunoassay in plasma samples obtained by drawing blood samples through indwelling atrial catheters. In SFO intact animals (n = 8) AII infusion (1.0 microgram/kg/min) resulted in increases in plasma OXY concentrations from baseline values of 6.8 +/- 2.5 pg/ml to postinfusion concentrations of 44.9 +/- 11.9 pg/ml. In a second series of experiments electrolytic lesions were placed in the region of the SFO prior to testing the effects of AII infusion on OXY concentrations. Two further experimental groups were thus established according to the histologically verified location of lesions in either the rostral or caudal SFO. In the caudal SFO lesioned group AII infusion resulted in increases in plasma OXY concentrations from control values of 6.9 +/- 1.4 pg/ml to postinfusion levels of 45.1 +/- 9.8 pg/ml. These changes were not significantly different from the SFO intact group. In contrast rostral SFO lesions resulted in significantly elevated basal concentrations of OXY (17.4 +/- 3.4 pg/ml, n = 6) while postinfusion concentrations were found to be 22.8 +/- 4.9 pg/ml indicating that AII infusion was without effect following such lesions. These data are in accordance with the hypothesis that circulating AII acts at the SFO to influence SFO efferents which in turn activate OXY secreting neurons in the hypothalamic supraoptic (SON) and paraventricular (PVN) nuclei. These neuroendocrine cells then release this peptide into the systemic circulation from the posterior pituitary.

The pathogenesis of the CNS manifestations of systemic lupus erythematosus (SLE) has been the subject of considerable investigation. The focus of many of these studies has concerned immune complex deposition within the choroid plexus (CP). Involvement of the other brain fenestrated vascular beds, the small, paraventricular circumventricular organs, has not been ascertained. For this purpose, chronic serum sickness, a good immunopathological experimental model of naturally occurring systemic immunological disorders such as SLE, was induced in Wistar rats by prolonged immunization with bovine serum albumin (BSA). The involvement of circumventricular vascular beds by immune deposits was ascertained immunohistochemically. The choroid plexus was found to be the most intensely involved circumventricular structure. Immune complex deposits were also present, in descending order of frequency, in the area postrema, subfornical organ, and pineal gland.

The subfornical organ (SFO) and surrounding periventricular tissue were ablated in sheep. Such a lesion did not significantly reduce water drinking in response to intracarotid, intravenous, or intracerebroventricular infusions of [Val5]angiotensin II amide (ANG II) but caused reduced intake of water in response to intracarotid infusion of hypertonic saline. The dipsogenic response of these sheep to water deprivation for 3 days was similar to that of normal sheep subjected to water deprivation. Although the results are not conclusive in excluding the SFO from having a role in ANG II-induced drinking, they show that there are receptors outside the SFO sensitive to blood-borne ANG II that are involved in water drinking in sheep. The results also show that tissue in the SFO or its surroundings may be involved in drinking caused by acute hypertonicity.

We investigated whether the increased intake of water during dietary electrolyte depletion is related to activation of the renin-angiotensin system. Young adult male rats were fed a low Na-, Cl-, K-free (low-salt) diet for 2 wk during which measurements were made of daily water intake and urine volume, plasma osmolality (Posm) and electrolytes, and plasma renin activity (PRA) and angiotensin I (ANG I) concentration. Water intake and urine output increased on day 3 of the low-salt diet, reached a maximum on day 4, and remained elevated, paralleling the time course of increases in PRA and ANG I plasma concentrations. Posm was normal after 2 days on the low-salt, although it was significantly lower by day 11. Renal concentrating ability was not different from controls after 6 days, but was significantly reduced after 11 days of treatment. Electrolytic lesions of the subfornical organ (SFO) abolished the low-salt diet-induced polydipsia, but had no effect on the diet-induced increases in PRA and plasma ANG I concentration. These data demonstrate that polydipsia induced by feeding a low-salt diet can develop in the presence of a normal or reduced Posm and precedes the development of a renal concentrating defect. The primary polydipsia is associated with elevated PRA and ANG I and appears to be mediated by angiotensin receptors in the SFO.

A tumour was found in the left ventricle of a 25 year-old woman. Histology of this "ependymoma of Monro's foramen" shows characteristic structures of the subfornical organ. Whereas tumours of the pituitary or the pineal gland, which are also part of the circumventricular organs, are quite frequent, a tumour with differentiation characteristic of the subfornical organ is a rarity.