Effect of electrolytic and chemical lesion by ibotenic acid of the septal area on water and salt intake

Water and sodium chloride intake was studied in male Holtzman rats weighing 250-300 g that had been subjected to electrolytic and chemical lesions of the septal area (SA). Water intake increased in animals with electrolytic lesion of the SA bilaterally from 169.37 +/- 8.55 (sham) to 214.87 +/- 23.10 ml/5 days (lesioned). Water intake decreased after ibotenic acid lesion of the SA from 229.33 +/- 27.60 to 127.33 +/- 22.84 ml/5 days. Sodium chloride intake (1.5%) increased in animals with electrolytic lesion of the SA from 10.0 +/- 1.73 to 15.5 +/- 1.95 ml/5 days after lesion. Also sodium chloride (1.5%) intake increased after ibotenic acid injection into the SA to a greater extent (from 7.83 +/- 1.25 to 14.33 +/- 1.87 ml/5 days). The results indicate that the water intake response may be due to lesions that involve cell bodies and fibers of passage and that the sodium intake response can also be induced by lesions which involve only cell bodies. Finally, these results led us to conclude that the SA uses its cell bodies and afferent bodies and fibers for processing inputs mediating water intake and salt appetite and that the cells bodies of the SA are implicated in increased water intake. (C) 1998 Elsevier B.V.

Activation of alpha(2)-adrenergic receptors into the lateral parabrachial nucleus enhances NaCl intake in rats

Water and NaCl intake is strongly inhibited by the activation of alpha(2)-adrenergic receptors with clonidine or moxonidine (alpha(2)-adrenergic/imidazoline agonists) injected peripherally or into the forebrain and by serotonin and cholecystokinin in the lateral parabrachial nucleus (LPBN). Considering that alpha(2)-adrenergic receptors exist in the LPBN and the similar origin of serotonergic and adrenergic afferent pathways to the LPBN, in this study we investigated the effects of bilateral injections of moxonidine alone or combined with RX 821002 (alpha(2)- adrenergic antagonist) into the LPBN on 1.8% NaCl and water intake induced by the treatment with s.c. furosemide (10 mg/kg)+captopril (5 mg/kg). Additionally, we investigated if moxonidine into the LPBN would modify furosemide+captopril-induced c-fos expression in the forebrain. Male Holtzman rats with cannulas implanted bilaterally in the LPBN were used. Contrary to forebrain injections, bilateral LPBN injections of moxonidine (0.1, 0.5 and 1 nmol/0.2 mul) strongly increased furosemide+captopril-induced 1.8% NaCl intake (16.6 +/- 2.7, 44.5 +/- 3.2 and 44.5 +/- 4.3 ml/2 h, respectively, vs. vehicle: 6.9 +/- 1.5 ml/2 h). Only the high dose of moxonidine increased water intake (23.3 +/- 3.8 ml/2 h, vs. vehicle: 12.1 +/- 2.6 ml/2 h). Prior injections of RX 821002 (10 and 20 nmol/0.2 mu1) abolished the effect of moxonidine (0.5 nmol) on 1.8% NaCl intake. Moxonidine into the LPBN did not modify furosemide+captopril-induced c-fos expression in forebrain areas related to the control of fluid-electrolyte balance. The results show that the activation of LPBN a2-adrenergic receptors enhances furosemide+captopril-induced 1.8% NaCl and water intake. This enhancement was not related to prior alteration in the activity of forebrain areas as suggested by c-fos expression. Previous and present results indicate opposite roles for alpha(2-)adrenergic receptors in the control of sodium and water intake according to their distribution in the rat brain. (C) 2004 IBRO. Published by Elsevier Ltd. All rights reserved.

Serotonergic mechanisms of the lateral parabrachial nucleus on DOCA-induced sodium intake

It has been shown that the serotonergic mechanisms of the lateral parabrachial nucleus (LPBN) inhibit NaCl intake in different models of angiotensin II (ANG II)-dependent NaCl intake in rats. However, there is no information about the involvement of LPBN serotonergic mechanisms on NaCl intake in a model of NaCl intake not dependent on ANG II like deoxycorticosterone (DOCA)-induced NaCl intake. Therefore, in this study we investigated the effects of bilateral injections of serotonergic agonist and antagonist into the LPBN on DOCA-induced 1.8% NaCl intake in rats. Male Holtzman rats were treated with s.c. DOCA (10 mg/rat each every 3 days). After a period of training, in which the rats had access to 1.8% NaCI during 2 h for several days, the rats were implanted with stainless steel cannulas bilaterally into the LPBN. Bilateral injections of the serotonergic receptor antagonist methysergide (4 mug/0.2 mul each site) in the LPBN increased 1.8% NaCI intake (32.2+/-3.9 versus vehicle: 15.0+/-1.6 ml/2 h, n = 10) and water intake (11.5+/-3.5 versus vehicle: 3.2+/-1.0 ml/2 h). Injections of the serotonergic 5HT(2A/2C) receptor agonist DOI (5 mug/0,2 mul each site) in the LPBN reduced 1.8% NaCl intake (6.8+/-1.7 versus saline: 12.4+/-1.9 ml/2 h, n = 10) and water intake (2.2+/-0.8 versus saline: 4.4+/-1.0 ml/2 h). Besides the previously demonstrated importance for the control of ANG II-dependent water and NaCl intake, the data show that the serotonergic inhibitory mechanisms of the LPBN are also involved in the control of DOCA-induced NaCl intake. (C) 2000 Elsevier B.V. B.V. All rights reserved.

Ingestion of hypertonic NaCl vs. palatable drinks by sodium-depleted rats

This work investigated whether the preference for NaCl solution is shifted to more palatable solutions in the adult male sodium-depleted rat (n=6-10 per group). Animals had daily access to three bottles, one containing water, another 1.8% NaCl (300 mM), and a third containing 0.9% NaCl (150 mM), Gatorade (orange-OG or grape flavored-GG), orange juice (sweetened or unsweetened, from concentrate), or 10% sucrose (no sodium). Sodium content in Gatorade and orange juice ranged from 7 to 14 mEq/l. Daily intakes were recorded for at least 5 days prior to sodium depletion. Then, the animals were depleted of sodium (diuretic plus sodium-deficient diet and water for 24 h). Then, the other two bottles were returned to the animals and the intakes were recorded for 120 min (sodium preference test, SPT). Daily intake from the third bottle (except for unsweetened orange juice) at least doubled the daily 1.8% NaCl intake. The average 1.8% NaCl intake (13 +/- 2 ml) in the SPT was higher than the intake of 10% sucrose (6 +/- 1 ml) or of any other solution (less than 6 ml). The intakes of 1.8% NaCl and 0.9% NaCl (10 +/- 3 ml) were similar during the SPT. The animals also preferred 0.9% NaCl (27 +/- 1 ml) to OG (3 +/- 1 ml) in the absence of 1.8% NaCl in the SPT. Therefore, the preference for sodium in sodium-depleted rats also applies when palatable and nutritive solutions are simultaneously available. (C) 2002 Elsevier B.V. All rights reserved.

Brain serotonin blockade and paradoxical salt intake in rats

Serotonin antagonism in the lateral parabrachial nucleus (LPBN) enhances sodium appetite induced by hypovolaemia and angiotensin-mineralocorticoid activation, but produces no sodium intake in euhydrated animals. In the present work, male adult rats (n=21) that received bilateral injections of the serotonergic antagonist methysergide (4 mug/ 0.2 mul) into the LPBN combined to intragastric load of 2 M NaCl (2 ml/rat), ingested hypertonic NaCl (ingestion of 4.3+/-1.6 ml/2 h of 0.3 M NaCl versus vehicle into LPBN: 0.2+/-0.2 ml/2 h, P<0.05). Methysergide- and vehicle-treated animals also ingested water (9.5+/-0.7 and 7.2+/-0.5 ml/2 h, respectively, P>0.05) as expected from the state of cell dehydration produced by the load. Ingestion of water (11.0+/-1.2 ml/2 h), and of 0.3 M NaCl (1.1+/-0.7 ml/2 h) were not altered by methysergide in NaCl loaded rats with misplaced LPBN injections (n=15). The ingestion of hypertonic NaCl by rats with serotonergic blockade in the LPBN suggests that the circuits subserving sodium appetite are activated, but at the same time strongly inhibited through the LPBN, during cell dehydration. (C) 2003 IBRO. Published by Elsevier Ltd. All rights reserved.

Serotonergic mechanism of the lateral parabrachial nucleus and relaxin-induced sodium intake

It has been shown that central or peripheral injections of the peptide relaxin induces water intake, not sodium intake in rats. Important inhibitory mechanisms involving serotonin and other neurotransmitters in the control of water and NaCl intake have been demonstrated in the lateral parabrachial nucleus (LPBN). In the present Study, we investigated the effects of bilateral injections of methysergide (serotonergic receptor antagonist) into the LPBN on intracerebroventricular (i.c.v.) relaxin-induced water and NaCl intake in rats. Additionally, the effect of the blockade of central angiotensin AT(1) receptors with i.c.v. losartan on relaxin-induced water and NaCl intake in rats treated with methysergide into the LPBN was also investigated. Male Holtzman rats with cannulas implanted into the lateral ventricle (LV) and bilaterally in the LPBN were used. Intracerebroventricular injections of relaxin (500 ng/l mul) induced water intake (5.1+/-0.7 ml/120 min), but not significant 1.8% NaCl intake (0.5+/-0.4 ml/120 min). Bilateral injections of methysergide (4 mug/0.2 mul) into the LPBN strongly stimulated relaxin-induced 1.8% NaCl intake (34.5+/-10.9 ml/120 min) and slightly increased water intake (10.5+/-4.9 ml/120 min). The pretreatment with i.c.v. losartan (100 mug/l mul) abolished the effects of i.c.v. relaxin combined with LPBN methysergide on 1.8% NaCI intake (0.5+/-0.4 ml/120 min). Losartan (100 mug/l mul) also abolished relaxin-induced water intake in rats injected with methysergide into the LPBN (1.6+/-0.8 ml/120 min) or not (0.5+/-0.3 ml/120 min). Losartan (50 mug/l mul) partially reduced the effects of relaxin. The results show that central relaxin interacting with central angiotensinergic mechanisms induces NaCl intake after the blockade of LPBN serotonergic mechanisms. (C) 2004 Elsevier B.V. All rights reserved.

Alpha(2)-adrenergic activation in the lateral parabrachial nucleus induces NaCi intake under conditions of systemic hyperosmolarity

The inhibition of sodium intake by increased plasma osmolarity may depend on inhibitory mechanisms present in the lateral parabrachial nucleus. Activation of alpha(2)-adrenergic receptors in the lateral parabrachial nucleus is suggested to deactivate inhibitory mechanisms present in this area increasing fluid depletion-induced 0.3 M NaCl intake. Considering the possibility that lateral parabrachial nucleus inhibitory mechanisms are activated and restrain sodium intake in animals with increased plasma osmolarity, in the present study we investigated the effects on water and 0.3 M NaCl intake produced by the activation of alpha(2)-adrenergic receptors in the lateral parabrachial nucleus in rats with increased plasma osmolarity. Male Holtzman rats with stainless steel cannulas implanted bilaterally into the lateral parabrachial nucleus were used. One hour after intragastric 2 M NaCl load (2 ml), bilateral injections of moxonidine (alpha(2)-adrenergic/imidazoline receptor agonist, 0.5 nmol/0.2 mu l, n=10) into the lateral parabrachial nucleus induced a strong ingestion of 0.3 M NaCl intake (19.1 +/- 5.5 ml/2 h vs. vehicle: 1.8 +/- 0.6 ml/2 h), without changing water intake (15.8 +/- 3.0 ml/2 h vs. vehicle: 9.3 +/- 2.0 ml/2 h). However, moxonidine into the lateral parabrachial nucleus in satiated rats not treated with 2 M NaCl produced no change on 0.3 M NaCl intake. The pre-treatment with RX 821002 (alpha(2)-adrenergic receptor antagonist, 20 nmol/0.2 mu l) into the lateral parabrachial nucleus almost abolished the effects of moxonidine on 0.3 M NaCl intake (4.7 +/- 3.4 ml/2 h). The present results suggest that alpha(2)-adrenergic receptor activation in the lateral parabrachial nucleus blocks inhibitory mechanisms, thereby allowing ingestion of hypertonic NaCl under conditions of extracellular hyperosmolarity. We suggest that during cell dehydration, circuits subserving sodium appetite are activated, but at the same time strongly inhibited through the lateral parabrachial nucleus. (c) 2006 IBRO. Published by Elsevier Ltd. All rights reserved.

Participation of alpha-1 and alpha-2 adrenoceptors of the lateral hypothalamic area in water intake, and renal sodium, potassium and urinary Volume excretion induced by central administration of angiotensin II

The circumventricular structures and the lateral hypothalamus (LH) have been shown to be important for the central action of angiotensin II (ANGII) on water and electrolyte regulation. Several anatomical findings have demonstrated neural connection between circumventricular structures and the LH, the present experiments were conducted to investigate the role of the alpha-adrenergic antagonists and agonistic injected into the LH on the water intake, sodium and potassium excretion elicited by injections of ANGII into the lateral ventricle (LV), the water intake was measured every 30 min over a period of 120 min. The sodium, potassium and urinary volume were measured over a period of 120 min in water-loaded rats. The injection of ANGII into the LV increased the water intake, which was reduced by previous injection of clonidine (an alpha-2-adrenergic agonist) into the LH. The injection of yohimbine (an alpha-2-adrenergic antagonist) and prazosin (an alpha-l-adrenergic antagonist) into the LH, which was done before injecting ANGII into the LV, also reduced the water intake induced by ANGII. The injection of ANGII into the LV reduced the sodium, potassium and urinary volume. Previous treatment with clonidine attenuated the action of ANGII in reducing the sodium, potassium and urinary volume, whereas previous treatment with yohimbine attenuated the effects of ANGII but with less intensity than that caused by clonidine. Previous treatment with prazosin increased the inhibitory effects of ANGII in those parameters. The injection of yohimbine and prazosin, which was done before the injection of clonidine, attenuated the effect of clonidine on the ANGII mechanism. The results of this study led us to postulate that when alpha-2-adrenergic receptors are blocked, the clonidine may act on the imidazoline receptors to produce its effects on the ANGII mechanism. We may also conclude that the LH is involved with circumventricular structures, which present excitatory and inhibitory mechanisms. Such mechanisms are responsible for regulating the renal excretion of sodium, potassium and water, (C) 2000 Elsevier B.V.

Moxonidine and central alpha(2) adrenergic receptors in sodium intake

Central injections of the alpha(2) adrenergic/imidazoline receptor agonist moxonidine inhibit water and NaCl intake in rats. In the present study, we investigated the possible involvement of central alpha(2) adrenergic receptors on the inhibitory effect of moxonidine in 0.3 M NaCl intake induced by 24 h sodium depletion. Male Holtzman rats with stainless-steel cannulas implanted into the lateral ventricle (LV) were used. Sodium depletion was produced by the treatment with the diuretic furosemide (20 mg/kg of body weight) injected subcutaneously + 24 h of sodium-deficient diet. Intracerebroventricular (icv) injections of moxonidine (20 nmol/l mul) reduced sodium depletion-induced 0.3 M NaCl intake (6.6 +/- 1.9 ml/120 min vs. vehicle: 12.7 +/- 1.7 ml/120 min). Pre-treatment with the alpha(2) adrenoreceptor antagonists RX 821002 (80 nmol/l mul), SK&F 86466 (640 nmol/l mul) and yohimbine (320 nmol/3 mul) injected icv abolished the inhibitory effect of icv moxonidine on sodium depletion-induced 0.3 M NaCl intake (13.3 +/- 1.4, 15.7 +/- 1.7 and 11.8 +/- 2.2 ml/120 min, respectively). The results show that the activation of alpha(2) adrenoreceptors is essential for the inhibitory effect of central moxonidine on sodium depletion-induced NaCl intake. (C) 2003 Elsevier B.V. All rights reserved.

L-Type calcium channels mediate water intake induced by angiotensin injection into median preoptic nucleus

Calcium ions are widely accepted as critically important in responses of neurons to a stimulus. We have show previously the central involvement of angiotensin II (ANGII) in water intake. This study determined whether voltage-dependent calcium channels are involved in ANGII-induced behavioral drinking implicating nitrergic mechanism. The antidipsogenic actions of L-type calcium channel antagonists nifedipine, on ANGII-induced drinking behavior were studied when it is injected into the median preoptic nucleus (MnPO). The influence of nitric oxide (NO) on nifedipine antidipsogenic action was also studied by utilizing the N-W-nitro-L-arginine methyl ester (L-NAME) a constitutive nitric oxide synthase inhibitor constitutive (cNOSI) and 7-nitroindazol (7-NIT) a specific neuronal nitric oxide synthase inhibitor (nNOSI) and L-arginine a NO donor. Rats 200-250 g, with cannulae implanted into MnPO, pre-treated into MnPO with either nifedipine, followed by ANGII, drank significantly less water than controls during the first 15 min after injection. However, L-NAME potentiated the dipsogenic effect of ANGII that is blocked by prior injection of nifedipine and L-arginine. 7-NIT injected prior to ANGII into MnPO also potentiated the dipsogenic effect of ANGII but with a less intensity than L-NAME that it is also blocked by prior injection of nifedipine. The results described in this paper provide evidence that calcium channels play important roles in the ANGII-induced behavioral water intake. The structures containing NO in the brain such as MnPO include both endothelial cells and neurons might be responsible for the influence of nifedipine on dipsogenic effect of ANGII. These data shows the correlation between L-type calcium channel and a free radical gas NO produced endogenously from amino acids L-arginine by endothelial and neuronal NO synthase in the control of ANGII-dipsogenic effect. This suggests that an L-type calcium channel participates in both short- and longer-term neuronal actions of ANGII by nitrergic way. (c) 2006 Elsevier B.V. All rights reserved.

Effects of V-1 and angiotensin receptor subtypes of the paraventricular nucleus on the water intake induced by vasopressin injected into the lateral septal area

In this study, we investigated the influence of d(CH2)(5)-Tyr (Me)-AVP (AAVP) an antagonist of V-1 receptors of arginine(8)-vasopressin (AVP) and the effects of losartan and CGP42112A (selective ligands of the AT, and AT, angiotensin receptors, respectively) injections into the paraventricular nucleus (PVN) on the thirst effects of AVP stimulation of the lateral septal area (LSA). AVP injection into the LSA increased the water intake in a dose-dependent manner. AAVP injected into the PVN produced a dose-dependent reduction of the drinking responses elicited by LSA administration of AVP. Both the AT(1) and AT(2) ligands administered into the PVN elicited a concentration-dependent inhibition in the water intake induced by AVP injected into the LSA, but losartan was more effective than CGP42112A the increase in the AVP response. These results indicate that LSA dipsogenic effects induced by AVP are mediated primarily by PVN AT(1) receptors. However, doses of losartan were more effective when combined with CGP42112A than when given alone, suggesting that the thirst induced by AVP injections into LSA may involve activation of multiple angiotensin II (ANG II) receptor subtypes. These results also suggests that facilitatory effects of AVP on water intake into the LSA are mediated through the activation of V-receptors and that the inhibitory effect requires V-receptors. Based on the present findings, we suggest that the administration of AVP into the LSA may play a role in the PVN control of water control. (C) 2003 Elsevier B.V. All rights reserved.

Effects of subtypes of adrenergic and angiotensinergic antagonists on the water and sodium intake induced by adrenaline injected into the paraventricular nucleus

The present experiments were conducted to investigate die role of the alpha(1A)-, alpha(1B)-, beta(1)-, beta(2)-adrenoceptors, and the effects of losartan and CGP42112A (selective ligands of the AT(1) and AT(2) angiotensin receptors, respectively) on the water and sodium intake elicited by paraventricular nucleus (PVN) injection of adrenaline. Male Holtzman rats with a stainless steel cannula implanted into the PVN were used. The ingestion of water and sodium was determined in separate groups submitted to water deprivation or sodium depletion with the diuretic furosemide (20 mg/rat). 5-Methylurapidil (an alpha(1A)-adrenergic antagonist) and ICI-118,551 (a beta(2)-adrenergic antagonist) injected into the PVN produced a dose-dependent increase, whereas cyclazosin (an alpha(1B)-adrenergic antagonist) and atenolol (a beta(1)-adrenergic antagonist) do not affect the inhibitory effect of water intake induced by adrenaline. on the other hand, the PVN administration of adrenaline increased the sodium intake in a dose-dependent manner. Previous injection of the alpha(1A) and beta(1) antagonists decreased, whereas injection of the alpha(1B) and beta(2) antagonists increased the salt intake induced by adrenaline. In rats with several doses of adrenaline into PVN, the previous administration of losartan increased in a dose-dependent manner the inhibitory effect of adrenaline and decreased the salt intake induced by adrenaline, while PVN CGP42112A was without effect. These results indicate that both appetites are mediated primarily by brain AT(1) receptors. However, the doses of losartan were more effective when combined with the doses of CGP42112A than given alone p < 0.05, suggesting that the water and salt intake effects of PVN adrenaline may involve activation of multiple angiotensin II (ANG II) receptors subtypes. (C) 2003 Elsevier B.V. All rights reserved.

Lateral hypothalamus lesions influences water and salt intake, and sodium and urine excretion, and arterial blood pressure induced by L-NAME and FK 409 injections into median preoptic nucleus in conscious rats

Male Holtzman rats weighting 200-250 g were anesthetized with zoletil 50 mg/Kg (tiletamine chloridrate 125,0 mg and zolazepan chloridrate 125,0 mg) into quadriceps muscle and submitted an electrolytic lesion of the lateral hypothalamus (LH) and a stainless steel cannula was implanted into their median preoptic nucleus (MnPO). We investigated the effects of the injection into the (MnPO) of FK 409 (20 mug/0.5 mul), a nitric oxide (NO) donor, and N-W-nitro-L-arginine methyl ester (L-NAME) 40 mug/0.5 mul, a nitric oxide synthase inhibitor (NOSI), on the water and sodium appetite and the natriuretic, diuretic and cardiovascular effects induced by injection of L-NAME and FK 409 injected into MnPO in rats with LH lesions. Controls were injected with a similar volume of 0.15 M NaCl. L-NAME injected into MnPO produced an increase in water and sodium intake and in sodium and urine excretion and increase de mean arterial pressure (MAP). FK 409 injected into MnPO did not produce any change in the hydro electrolytic and cardiovascular parameters in LH-sham and lesioned rats. FK 409 injected before L-NAME attenuated its effects. These data show that electrolytic lesion of the LH reduces fluid and sodium intake as well as sodium and urine excretion, and the pressor effect induced by L-NAME. LH involvement with NO of the MnPO excitatory and inhibitory mechanisms related to water and sodium intake, sodium excretion and cardiovascular control is suggested. (C) 2004 Elsevier B.V. All rights reserved.