Macrophage Migration Inhibitory Factor in the Paraventricular Nucleus Plays a Major Role in the Sympathoexcitatory Response to Salt

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Water deprivation-induced sodium appetite: humoral and cardiovascular mediators and immediate early genes

Adult rats deprived of water for 24-30 h were allowed to rehydrate by ingesting only water for 1-2 h. Rats were then given access to both water and 1.8% NaCl. This procedure induced a sodium appetite defined by the operational criteria of a significant increase in 1.8% NaCl intake (3.8 +/- 0.8 ml/2 h; n = 6). Expression of Fos (as assessed by immunohistochemistry) was increased in the organum vasculosum of the lamina terminalis (OVLT), median preoptic nucleus (MnPO), subfornical organ (SFO), and supraoptic nucleus (SON) after water deprivation. After rehydration with water but before consumption of 1.8% NaCl, Fos expression in the SON disappeared and was partially reduced in the OVLT and MnPO. However, Fos expression did not change in the SFO. Water deprivation also 1) increased plasma renin activity (PRA), osmolality, and plasma Na+; 2) decreased blood volume; and 3) reduced total body Na+; but 4) did not alter arterial blood pressure. Rehydration with water alone caused only plasma osmolality and plasma Na+ concentration to revert to euhydrated levels. The changes in Fos expression and PRA are consistent with a proposed role for ANG II in the control of the sodium appetite produced by water deprivation followed by rehydration with only water.

Serotonin and circadian rhythms

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Oxytocinergic and serotonergic systems involvement in sodium intake regulation: satiety or hypertonicity markers?

Previous studies demonstrated the inhibitory participation of serotonergic ( 5-HT) and oxytocinergic (OT) neurons on sodium appetite induced by peritoneal dialysis (PD) in rats. The activity of 5-HT neurons increases after PD- induced 2% NaCl intake and decreases after sodium depletion; however, the activity of the OT neurons appears only after PD-induced 2% NaCl intake. To discriminate whether the differential activations of the 5-HT and OT neurons in this model are a consequence of the sodium satiation process or are the result of stimulation caused by the entry to the body of a hypertonic sodium solution during sodium access, we analyzed the number of Fos-5-HT- and Fos-OT-immunoreactive neurons in the dorsal raphe nucleus and the paraventricular nucleus of the hypothalamus-supraoptic nucleus, respectively, after isotonic vs. hypertonic NaCl intake induced by PD. We also studied the OT plasma levels after PD- induced isotonic or hypertonic NaCl intake. Sodium intake induced by PD significantly increased the number of Fos-5- HT cells, independently of the concentration of NaCl consumed. In contrast, the number of Fos-OT neurons increased after hypertonic NaCl intake, in both depleted and nondepleted animals. The OT plasma levels significantly increased only in the PD- induced 2% NaCl intake group in relation to others, showing a synergic effect of both factors. In summary, 5-HT neurons were activated after body sodium status was reestablished, suggesting that this system is activated under conditions of satiety. In terms of the OT system, both OT neural activity and OT plasma levels were increased by the entry of hypertonic NaCl solution during sodium consumption, suggesting that this system is involved in the processing of hyperosmotic signals.

Effects of nitric oxide and arginine vasopressin on sodium intake induced by central angiotensin II. Part 2

We study the effects of angiotensin receptors antagonists, arginine vasopressin receptor antagonist, L-arginine and L-NAME, injected into supraoptic nucleus of the hypothalamus (SON) on sodium intake induced by the injection of angiotensin II (ANGII). Holtzman rats weighing 200-250 g with canulae implanted into the SON were used. The drugs were injected in 0.5 μL over 30-60 sec. Sodium intake after injection of saline SAL+SAL 0.15 M NaCl was 0.10±00.1 mL 2 h -1; SAL+ANGII injected into SON increased sodium intake. Losartan injected prior to ANGII into SON decreased sodium intake induced by ANGII. PD123319 injected prior to ANGII produced no changes in sodium intake induced by ANGII. AVPA receptor V 1 antagonist injected prior to ANGII reduced sodium intake with a less intensity than losartan. L-arginine injected prior to ANGII decreases sodium intake at a same intensity than losartan. L-NAME injected prior to ANGII potentiated sodium intake induced by ANGII. Losartan injected simultaneously with L-arginine prior to ANGII blocked the natriorexigenic effect of ANGII. These results confirm the importance of SON in the control of sodium intake. Also suggest that both AT 1 and arginine vasopressin V 1 receptors interact with nitrergic pathways within the SON influencing the sodium metabolism by changing sodium appetite induced by ANGII. © 2007 Asian Network for Scientific Information.

Effects of nitric oxide and arginine vasopressin on water intake induced by central angiotensin II. Part 1

We determined the effects of AT 1 and AT 2 (selective no peptides antagonists angiotensin receptors), arginine vasopressin V 1 receptor antagonist as well as L-arginine, a nitric oxide donor and N W-nitro-L-arginine methyl ester (L-NAME), a nitric oxide synthase inhibitor, injected into supraoptic nucleus (SON) on water and sodium intake induced by the injection of angiotensin II (ANGII). Male Holtzman rats weighing 200-250 g with canulae implanted into the SON were used. The drugs were injected in 0.5 μL over 30-60 sec. The water intake after injection of saline SAL+SAL 0.15 M NaCl was 0.40±0.1 mL 2 h -1; SAL+ANGII increase water intake. Losartan decreased the water intake induced by ANGII. PD123319 injected prior to produce no change in water intake induced by ANGII. AVPA prior to ANGII reduced the water intake with a less intensity than losartan. L-arginine prior to ANGII decreases the water intake at a same intensity than losartan. L-NAME prior to ANGII potentiated the dipsogenic effect of ANGII. Losartan injected simultaneously with L-arginine prior to ANGII blocked the dipsogenic effect of ANGII. These results confirm the importance of SON in the control of water intake and strongly suggest that AT 1, V 1 receptors interact with nitrergic pathways within the SON influencing the dipsogenic effect of ANGII.

Hypothalamic disconnection caudal to paraventricular nucleus affects cardiovascular and drinking responses to central angiotensin II and carbachol

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

The Edinger-Westphal nucleus II: Hypothalamic afferents in the rat

Numerous functions have been attributed to the Edinger-Westphal nucleus (EW), including those related to feeding behavior, pain control, alcohol consumption and the stress response. The EW is thought to consist of two parts: one controls accommodation, choroidal blood flow and pupillary constriction, primarily comprising cholinergic cells and projecting to the ciliary ganglion; and the other would be involved in the non-ocular functions mentioned above, comprising peptide-producing neurons and projecting to the brainstem, spinal cord and prosencephalic regions. Despite the fact that the EW is well known, its connections have yet to be described in detail. The aim of this work was to produce a map of the hypothalamic sources of afferents to the EW in the rat. We injected the retrograde tracer Fluoro-Gold into the EW, and using biotinylated dextran amine, injected into afferent sources as the anterograde control. We found retrogradely labeled cells in the following regions: subfornical organ, paraventricular hypothalamic nucleus, arcuate nucleus, lateral hypothalamic area, zona incerta, posterior hypothalamic nucleus, medial vestibular nucleus and cerebellar interpositus nucleus. After injecting BDA into the paraventricular hypothalamic nucleus, lateral hypothalamic area and posterior hypothalamic nucleus, we found anterogradely labeled fibers in close apposition to and potential synaptic contact with urocortin 1-immunoreactive cells in the EW. On the basis of our findings, we can suggest that the connections between the EW and the hypothalamic nuclei are involved in controlling stress responses and feeding behavior. © 2013 The Authors.

Catecholaminergic neurons in the comissural region of the nucleus of the solitary tract modulate hyperosmolality-induced responses

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Investigation of the hypothalamic defensive system in the mouse

The hypothalamus plays especially important roles in various endocrine, autonomic, and behavioral responses that guarantee the survival of both the individual and the species. In the rat, a distinct hypothalamic defensive circuit has been defined as critical for integrating predatory threats, raising an important question as to whether this concept could be applied to other prey species. To start addressing this matter, in the present study, we investigated, in another prey species (the mouse), the pattern of hypothalamic Fos immunoreactivity in response to exposure to a predator (a rat, using the Rat Exposure Test). During rat exposure, mice remained concealed in the home chamber for a longer period of time and increased freezing and risk assessment activity. We were able to show that the mouse and the rat present a similar pattern of hypothalamic activation in response to a predator. of particular note, similar to what has been described for the rat, we observed in the mouse that predator exposure induces a striking activation in the elements of the medial hypothalamic defensive system, namely, the anterior hypothalamic nucleus, the dorsomedial part of the ventromedial hypothalamic nucleus and the dorsal premammillary nucleus. Moreover, as described for the rat, predator-exposed mice also presented increased Fos levels in the autonomic and parvicellular parts of the paraventricular hypothalamic nucleus, lateral preoptic area and subfornical region of the lateral hypothalamic area. In conclusion, the present data give further support to the concept that a specific hypothalamic defensive circuit should be preserved across different prey species. (C) 2008 Elsevier B.V. All rights reserved.

HYPOTHALAMIC-LESIONS INCREASE SALINE INGESTION INDUCED BY INJECTION OF ANGIOTENSIN-II INTO AV3V IN RATS

Water and 3% NaCl intake were increased by the injection of 4 ng angiotensin II (ANG II) into the anteroventral third ventricle (AV3V) region of rats. Pretreatment with two specific ANG II receptor antagonists, [octanoyl-Leu8]ANG II and [Leu8]ANG II, significantly reduced ANG II-induced water and saline intake. This inhibition lasted approximately 30 min, with partial recovery at 60 min. In rats with electrolytic lesion of the bilateral ventromedial nucleus of hypothalamus (VMH), the effect of ANG II on water intake was not different from that observed in sham rats, but saline ingestion increased. In summary, the present results show that the AV3V region is an important central structure for ANG II-induced saline ingestion. Lesion of the VMH increases the response to ANG II, showing an interaction between the AV3V region and the VMH in the regulation of salt ingestion.

Renal effects of angiotensin II receptor subtype 1 and 2-selective ligands injected into the paraventricular nucleus of conscious rats

We determined the effects of losartan and CGP42112A (selective ligands of the AT1 and AT2 angiotensin receptors, respectively) and salarasin (a relatively nonselective angiotensin receptor antagonist) on urinary volume and urinary sodium and potassium excretion induced by administration of angiotensin II (ANG II) into the paraventricular nucleus (PVN) of conscious rats. Both the AT1 and AT2 ligands and salarasin administered in the presence of ANG II elicited a concentration-dependent inhibition of urine excretion, but losartan inhibited only 75% of this response. The IC50 for salarasin, CGP42112A, and losartan was 0.01, 0.05, and 6 nM, respectively. Previous treatment with saralasin, CGP42112A and losartan competitively antagonized the natriuretic responses to PVN administration of ANG II, and the IC50 values were 0.09, 0.48, and 10 nM, respectively. The maximum response to losartan was 65% of that obtained with saralasin. Pretreatment with saralasin, losartan, and CGP42112A injected into the PVN caused shifts to the right of the concentration-response curves, but the losartan concentrations were disproportionately greater compared with salarasin or CGP42112A. The IC50 values were 0.06, 0.5, and 7.0 for salarasin, CGP42112A, and losartan, respectively. These results suggest that both AT1 and AT2 receptor subtypes in the PVN are involved in ANG II-related urine, sodium, and potassium excretion, and that the inhibitory responses to AT2 blockade are predominant. Copyright (C) 1999 Elsevier Science B.V.

Haemodynamic effects of hypothalamic disconnection in anaesthetized rats

The aim of the present study was to analyse the haemodynamic effects induced by the hypothalamic disconnection (HD) caudal or rostral to the paraventricular nucleus of the hypothalamus (PVN). Mean arterial pressure (MAP), hindlimb, renal and mesenteric blood flow and vascular conductance (HVC, RVC and MVC, respectively) were measured in urethane (1.2 g/kg, i.v.) anesthetized rats for 60 min after disconnection. HD caudal to the PVN was performed with a double-edged microknife of bayonet shape (R=1 mm, H=2 mm) stereotaxically placed, lowered 2.8 mm caudal to the bregma along the midline. The cut was achieved by rotating the microknife 90° right and 90° left. HD rostral to the PVN was performed with the knife placed 0.8 mm caudal to the bregma. Thirty minutes after the hypothalamic disconnection caudal (HD-C), a decrease in MAP was observed (-14±3 mm Hg), reaching a 60-min decrease of 30±3 mm Hg. Hindlimb conductance increased 10 min after HD (156±14%) and remained elevated throughout the experimental period. On the contrary, we observed a transitory renal vasoconstriction (82±9%, ≤20 min) and a late mesenteric vasodilation, starting at 30 min (108±4%) and reaching 138±6% at 60 min. In rats with HD rostral to the PVN, we only observed minor changes in the cardiovascular parameters. In the MAP, there was a slight decrease 60 min after the hypothalamic disconnection rostral (HD-R) (-9±4 mm Hg). There were no significant changes in HVC. RVC and MVC were increased 60 min after the HD-R (116±12% and 124±11%, respectively). These results suggest that vasodilation in the hindlimb and in the mesenteric bed could contribute to the observed decrease in MAP in HD caudal to PVN rats. © 2002 Elsevier Science B.V. All rights reserved.

Influence of angiotensin II receptor subtypes of the paraventricular nucleus on the physiological responses induced by angiotensin II injection into the medial septal area

Objective - We determined the effects of losartan and PD 123319 (antagonists of the AT1 and AT2 angiotensin receptors, respectively), and [Sar1, Ala8] ANG II (a relatively peptide antagonist of angiotensin receptors) injected into the paraventricular nucleus (PVN) on water and 3% NaCl intake, and the diuretic, natriuretic, and pressor effects induced by administration of angiotensin II (ANG II) into the medial septal area (MSA) of conscious rats. Methods - Holtzman rats were used. Animals were anesthetized with tribromoethanol (20 mg) per 100 grams of body weight, ip. A stainless steel guide cannula was implanted into the MSA and PVN. All drugs were injected in 0.5-μl volumes for 10-15 seconds. Seven days after brain surgery, water and 3% NaCl intake, urine and sodium excretion, and arterial blood pressure were measured. Results - Losartan (40 nmol) and [Sar1, Ala8] ANG II (40 nmol) completely eliminated whereas PD 123319 (40 nmol) partially blocked the increase in water and sodium intake and the increase in arterial blood pressure induced by ANG II (10 nmol) injected into the MSA. The PVN administration of PD 123319 and [Sar1, Ala8] ANG II blocked whereas losartan attenuated the diuresis and natriuresis induced by MSA administration of ANG II. Conclusion - MSA involvement with PVN on water and sodium homeostasis and arterial pressure modulation utilizing ANGII receptors is suggested.

Mechanisms in the bed nucleus of the stria terminalis involved in control of autonomic and neuroendocrine functions: A review

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