Preoptic angiotensin and salt appetite.

Two experiments were designed to test whether angiotensin (ANG) synthesis or receptor activation in the ventral preoptic region is critical for ANG-induced salt appetite in rats. In Experiment 1, infusions of ANG into the subfornical organ (SFO) produced water drinking without saline intake, but infusions near the organum vasculosum laminae terminals (OVLT) produced both water and saline drinking. Thus, forebrain areas that support water drinking to ANG do not all support salt appetite. In Experiment 2, rats were given oral captopril (CAP) to enhance daily intake of water and saline solution by increasing ANG II synthesis in the brain. CAP microinjected into the SFO reduced CAP-enhanced water drinking without affecting saline intake, but CAP in the OVLT reduced enhanced saline intake without affecting water drinking. Thus, ANG acting in the OVLT, the most ventral part of the median preoptic nucleus, or other nearby structures is important for ANG-induced saline appetite. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

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)     

Influence of salt intake, ANG II synthesis and SFO lesion on thirst and blood pressure during sodium depletion. Subfornical organ

Water intake was elevated in sodium-depleted rats during a daytime salt appetite test, but other rats drank a similar amount of water when saline was not available for drinking during the test. This water intake stimulated by sodium depletion was blocked by an inhibition of angiotensin (ANG) II synthesis with a high dose of captopril (100 mg/kg, sc). Captopril did not reduce water intake by causing hypotensive shock or uremia, because water and saline intakes were increased rather than decreased after a low dose of captopril (5 mg/kg) that also reduced blood pressure and elevated blood urea nitrogen. The water intake, but not salt appetite, induced by sodium depletion was greatly reduced by a lesion of the subfornical organ (SFO) in one-bottle tests, and this was not clearly related to any effects of the lesion on blood pressure. A physiological role for ANG II in water intake induced by sodium depletion has recently been disputed, but the simplest explanation for the data remains that elevated levels of circulating ANG II bind to receptors in the SFO to generate daytime water drinking during sodium depletion.     

Subfornical organ connectivity and drinking to captopril or carbachol in rats.

These experiments were conducted to test whether drinking to ip captopril or to intraventricular carbachol requires an intact fiber system from the ventral subfornical organ (SFO). Wire-knife cuts were made through the wall of the third ventricle ventral to the SFO. Control rats had either sham lesions or histologically identified missed cuts. Rats with good cuts (a) drank less than either control group after ip injections of 4 mg/kg captopril, (b) drank normal amounts of 0.3 M NaCl solution when captopril was placed in the drinking water at 0.1 rag/ml, (c) drank less water but a normal amount of saline after 6 mg/kg captopril ip and 10 mg/kg furosemide diuretic ip, and (d) drank normal amounts of water after lateral ventricular injections of 1.2 or 4 nmol of carbachol. The results of the captopril experiments confirm predictions based on studies of SFO lesions and suggest that captopril causes water, but not saline, drinking via an angiotensin-related mechanism acting at the SFO. The carbachol experiment indicates either that the SFO is not a unique receptor site for ventricular carbachol or that the fibers mediating this response do not require the pathways through the ventral pole of the SFO. (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.     

Ethanol-induced changes in plasma proteins, angiotensin II, and salt appetite in rats.

Sodium depletion in rats elicits a sodium appetite that results from a cerebral action of angiotensin II (ANG II) and aldosterone. Alcohol also activates the renin-angiotensin system, but the mechanism is poorly understood and not related to sodium excretion. In this study, 2.5 g/kg intraperitoneal/ly (ip) ethanol produced a 20% decline in plasma volume and plasma protein concentration 1–2 hrs and elicited salt appetite beginning in 3–4 hrs. Blockade of ANG II synthesis in the brain and periphery with the angiotensin-converting enzyme inhibitor captopril eliminated the thirst and salt appetite. Peripheral captopril alone enhanced fluid intake, which indicated that alcohol elevated renin secretion. Ethanol-induced suppression of hepatic plasma protein secretion and the consequent fall in plasma colloid osmotic pressure apparently resulted in hypovolemia and renin secretion, which then produced thirst and salt appetite through an action of ANG II on the brain. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

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)     

Diminished salt appetite in spontaneously hypertensive rats following local administration of the angiotensin II antagonist saralasin in the median preoptic area

Previous studies have suggested that angiotensin (ANG) synthesis, receptor activation, or both, in the median preoptic nucleus (MnPO) are responsible for initiating ANG-related salt appetite in normotensive rats. The present study was designed to test whether treatment with saralasin (Sar), an ANG II antagonist, in the MnPO area causes changes in saline (0.3 M NaCl solution) and water intakes in the spontaneously hypertensive rat (SHR), which is known to show greater salt appetite compared to normotensive Wistar-Kyoto (WKY) rats. Treatment with Sar in the MnPO area produced significantly attenuated saline intake, but had no effect on water intake. The results may support the importance of the ANG system in the MnPO area for salt appetite, and suggest that a disorder in the system may cause abnormal salt intake in SHR.     

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.     

Forebrain lesions differentially affect drinking elicited by dipsogenic challenges and injections of muscimol into the median raphe nucleus.

Injections of muscimol into the median raphe nucleus (MR) elicit intense drinking in normally hydrated rats. To determine whether this response is dependent on forebrain systems mediating other aspects of water intake, the authors examined the effects of lesions of the subfornical organ (SFO), median preoptic nucleus (MnPO), lateral preoptic area (LPO), or lateral hypothalamus (LH) on the drinking. Lesions of the SFO or LH attenuated muscimol-elicited drinking, whereas lesions of the MnPO or LPO increased water intake after the treatment. All of the lesion groups showed a deficit in drinking to injections of polyethylene glycol and at least one of the doses of hypertonic saline. Only the SFO- and LH-lesioned groups showed a suppression of drinking to systemic injections of angiotensin II, suggesting that the drinking elicited by intra-MR injections of muscimol may involve changes in the central circuits mediating angiotensin-induced drinking. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Salt appetite and lesions of the ventral part of the ventral median preoptic nucleus.

Angiotensin receptors in the most ventral part of the ventral median preoptic nucleus (VVMnPO) or organum vasculosum laminae terminalis appear to be important for salt appetite to angiotensin in rats. If so, then small lesions of this region should reduce salt appetite that is dependent on angiotensin. In separate experiments, the lesion greatly reduced salt appetite after treatments with chronic oral captopril or sodium depletion. On the other hand, the VVMnPO lesion actually enhanced salt appetite to deoxycorticosterone acetate. The lesion did not affect water intake to water deprivation, combined food-water deprivation, isoproterenol, or hypertonic saline, and basal plasma osmolality and sodium values were normal. These experiments suggest that VVMnPO lesions selectively affect angiotensin-induced salt appetite without producing the gross hydrational deficits that occur with larger lesions of the ventral forebrain. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

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)     

Localization of receptors for the dipsogenic action of angiotensin II in the subfornical organ of rats.

Investigated the proposal that the subfornical organ (SFO) is a site of receptors for drinking induced by angiotensin II (AII). A total of 159 male albino Holtzman rats was used. Intracranial injections of physiological doses of AII elicited drinking if and only if applied directly to the SFO (Exp I). Ablation of the SFO selectively (Exp II) and permanently (Exp IV) eliminated drinking elicited by physiological doses of iv infused AII. Animals in which SFO had been ablated responded normally to cellular dehydration but reduced responding to the extracellular thirsts of beta-adrenergic activation and hyperoncotic colloid dialysis (Exp III). Infusion of saralasin, an AII antagonist, directly into the SFO selectively and reversibly antagonized iv AII drinking (Exp V). The hypothesis that the SFO contains dipsogenic receptors for circulating AII was supported. (2 p ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Role of angiotensin II and vasopressin receptors within the supraoptic nucleus in water and sodium intake induced by the injection of angiotensin II into the medial septal area

In this study we investigated the effects of the injection into the supraoptic nucleus (SON) of non-peptide AT1- and AT2-angiotensin II (ANG II) receptor antagonists, DuP753 and PD123319, as well as of the arginine-vasopressin (AVP) receptor antagonist d(CH2)5-Tyr(Me)-AVP, on water and 3% NaCl intake induced by the injection of ANG II into the medial septal area (MSA). The effects on water or 3% NaCl intake were assessed in 30-h water-deprived or in 20-h water-deprived furosemide-treated adult male rats, respectively. The drugs were injected in 0.5 microliter over 30-60 s. Controls were injected with a similar volume of 0.15 M NaCl. Antagonists were injected at doses of 20, 80 and 180 nmol. Water and sodium intake was measured over a 2-h period. Previous administration of the AT1 receptor antagonist DuP753 into the SON decreased water (65%, N = 10, P < 0.01) and sodium intake (81%, N = 8, P < 0.01) induced by the injection of ANG II (10 nmol) into the MSA. Neither of these responses was significantly changed by injection of the AT2-receptor antagonist PD123319 into the SON. On the other hand, while there was a decrease in water intake (45%, N = 9, P < 0.01), ANG II-induced sodium intake was significantly increased (70%, N = 8, P < 0.01) following injection of the V1-type vasopressin antagonist d(CH2)5-Tyr(Me)-AVP into the SON. These results suggest that both AT1 and V1 receptors within the SON may be involved in water and sodium intake induced by the activation of ANG II receptors within the MSA. Furthermore, they do not support the involvement of MSA AT2 receptors in the mediation of these responses.     

Bradykinin suppresses alcohol intake and plays a role in the suppression produced by an ACE inhibitor

The possible role of the endogenous kinins in the control of alcohol intake was assessed in two experiments. In Experiment 1, naive rats, maintained on ad lib food and water, were given daily 40-min access to a 6% (w/v) alcohol solution and water. Daily intraperitoneal (IP) injections of captopril (20 mg/kg) significantly reduced alcohol intake, while pretreatment with subcutaneous (SC) injections of the bradykinin antagonist [D-Phe7]-bradykinin (100-300 micrograms/kg) attenuated the suppressive effect of captopril on alcohol intake. The saline vehicle or the bradykinin antagonist alone did not alter alcohol intake. In Experiment 2, bradykinin was administered daily at 100, 200, and 400 micrograms/kg doses SC either alone or in combination with captopril 10 mg/kg IP. Neither bradykinin nor captopril by themselves changed alcohol or water intake. Bradykinin combined with captopril stimulated water intake and reduced alcohol intake by up to 70%. This effect was not due to drug-induced changes in the pharmacokinetics of alcohol. The angiotensin II receptor antagonist [Sar1,Thr8]-angiotensin II at 250 and 500 micrograms/kg SC attenuated the stimulation of water intake but not the reduction in alcohol intake. It is suggested that by inhibiting kininase II, ACE inhibitors extend the duration of action of bradykinin and thereby unmask a potent inhibition of alcohol intake mediated by kinins--an effect that is dissociable from the accompanying stimulation of water intake. Taken together, these results point to an involvement of the kinin system in the regulation of alcohol intake and in particular to a role of bradykinin in the suppressive effect of ACE inhibitors on alcohol intake.     

Comparison of the effects of the dipeptidyl peptidase inhibitors captopril, ramipril, and enalapril on water intake and sodium appetite of Sprague-Dawley rats.

Two experiments were performed with rats to study the effects of different inhibitors of angiotensin I (Ang I) converting enzyme on water intake and sodium appetite. Subcutaneous administration of low doses of either enalapril or ramipril, like captopril, was dipsogenic. Acute administration of ramipril also enhanced the drinking response to peripherally administered Ang I. Higher doses inhibited the drinking response to Ang I, administered acutely peripherally or centrally. Data provide behavioral evidence that enalapril and ramipril inhibit brain converting enzyme activity and are considerably more potent than captopril. All 3 compounds, administered chronically in food, induced an appetite for NaCl solution. Enalapril and ramipril were more potent than captopril. Plasma renin activity was increased by each of these inhibitors, but the magnitude of the increase was not clearly related to the amount of NaCl consumed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Mutual interactions between HIV-1 and cytokines in adherent cells during acute infection

Intracerebroventricular (i.c.v.) infusions of angiotensin II (AII) reliably induced c-fos expression in the supraoptic (SON) and paraventricular (PVN) nuclei, as well as other areas of the basal forebrain including the OVLT, subfornical organ (SFO), and bed nucleus (BNST). Double-labelling showed that AII-induced c-fos was observed in both vasopressin (AVP-) and oxytocin (OXY)-containing neurons of the SON and PVN in male rats. Allowing rats to drink water after AII infusions suppressed c-fos expression both AVP- and OXY-stained magnocellular neurons. Intragastric infusions of water were also effective, showing that oro-pharyngeal stimuli were not critical. Maximal suppression occurred in rats in whom water had been infused intragastrically about 5 min before i.c.v. AII infusions, suggesting that changes in osmolarity were responsible. i.c.v. AII also induced c-fos expression in a number of brainstem structures, including the solitary nucleus (NTS), lateral parabrachial nucleus (LPBN), locus coeruleus (LC), and the area postrema (AP). These results indicate that AVP and OXY-containing neurons in the magnocellular parts of the SON and PVN alter their immediate-early gene response to AII after water intake, and that this does not depend upon oro-pharyngeal factors. Furthermore, AII can induce c-fos expression in a number of brainstem nuclei associated with autonomic function, and these do not respond to water intake.     

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)     

Increased sodium appetite and thirst in rat induced by the ingredients of liquorice, glycyrrhizic acid and glycyrrhetinic acid

In the rat, blocking 11 beta-OHSD with the active ingredient of liquorice, glycyrrhizic acid (GZA) or its hydrolytic product, 18 beta-glycyrrhetinic acid (GTA), caused potassium loss, increased water intake and a primary increase in salt appetite that was specific for sodium and not secondary to sodium loss. Intracerebroventricular injection of angiotensin II enhanced the sodium appetite but carbachol did not. The stimulating effects of GZA or GTA on intakes of water and NaCl resembled those caused by the administration of excessive amounts of mineralocorticoid. The results suggest that GZA- or GTA-induced drinking behaviour is mediated by circulating glucocorticoids. After liquorice blockade of 11 beta-OHSD, the peripheral and central mineralocorticoid receptors are no longer protected from glucocorticoid action.     

Angiotensin and salt appetite: Physiological amounts of angiotensin given peripherally increase salt appetite in the rat.

In 2 experiments, adrenalectomized male Sprague-Dawley rats were maintained ad lib on distilled water, 3% saline, and sodium-free food. In Exp I, 45 Ss were given desoxycorticosterone acetate (DOCA [.1–2 mg/kg/day, intramuscularly]) for 5 days to determine the dose of DOCA that would produce the lowest voluntary saline intake, and 800 μg/kg/day was found to produce the nadir in saline intake. In Exp II, 40 Ss were placed ad lib on distilled water, saline, and sodium-free food as described above, maintained on 800 μg/kg/day DOCA, and infused with 4, 25, or 100 μg/kg/day angiotensin II (AII) or 0.9% saline. The 3 AII groups showed significant percentage changes in their saline intake above pre-AII levels; the saline control group showed no change in saline intake from pre-AII level. Results demonstrate the production of salt appetite in rats by peripheral administration of physiological doses of AII. (25 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)