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Renovascular hypertension is a type of secondary hypertension caused by renal artery stenosis, leading to an increase in the renin–angiotensin–aldosterone system (RAAS). Two-kidney, 1-clip (2K1C) is a model of renovascular hypertension in which rats have an increased sodium intake induced by water deprivation (WD), a common situation found in the nature. In addition, a high-sodium diet in 2K1C rats induces glomerular lesion. Therefore, the purpose of this study was to investigate whether angiotensin II (ANG II) and/or aldosterone participates in the increased sodium intake in 2K1C rats under WD. In addition, we also verified if central AT1 and mineralocorticoid receptor blockade would change the high levels of arterial pressure in water-replete (WR) and WD 2K1C rats, because blood pressure changes can facilitate or inhibit water and sodium intake. Finally, possible central areas activated during WD or WD followed by partial rehydration (PR) in 2K1C rats were also investigated. Male Holtzman rats (150–180 g) received a silver clip around the left renal artery to induce renovascular hypertension. Six weeks after renal surgery, a stainless-steel cannula was implanted in the lateral ventricle, followed by 5–7 days of recovery before starting tests. Losartan (AT1 receptor antagonist) injected intracerebroventricularly attenuated water intake during the thirst test. Either icv losartan or RU28318 (mineralocorticoid receptor antagonist) reduced 0.3 M NaCl intake, whereas the combination of losartan and RU28318 icv totally blocked 0.3 M NaCl intake induced by WD in 2K1C rats. Losartan and RU28318 icv did not change hypertension levels of normohydrated 2K1C rats, but reduced the increase in mean arterial pressure (MAP) produced by WD. c-Fos expression increased in the lamina terminalis and in the NTS in WD condition, and increased even more after WD-PR. These results suggest the participation of ANG II and aldosterone acting centrally in the enhanced sodium intake in WD 2K1C rats, and not in the maintenance of hypertension in satiated and fluid-replete 2K1C rats. [ABSTRACT FROM AUTHOR]

BACKGROUND Macrophage migration inhibitory factor (MIF) is an intracellular inhibitory regulator of the actions of angiotensin II in the central nervous system. Renovascular hypertensive 2-kidney, 1-clip (2K1C) rats have an increased activity of the renin-angiotensin system and a decrease in baroreflex function compared to normotensive (NT) rats. In the present study, we tested the effects of MIF overexpression within the nucleus of the solitary tract (NTS), a key brainstem region for cardiovascular regulation, on the development of hypertension, on baroreflex function, and on water and food intake in 2K1C rats. METHODS Holtzman NT rats received a silver clip around the left renal artery to induce 2K1C hypertension. Three weeks later, rats were microinjected in the NTS with AAV2-CBA-MIF, to increase the expression of MIF, or with the control vector AAV2-CBA-enhanced green fluorescent protein. Mean arterial pressure (MAP) and heart rate were recorded by telemetry. Baroreflex function was tested, and water and food intake were also measured. RESULTS Increasing MIF expression in the NTS of 2K1C rats attenuated the development of hypertension, reversed the impairment of baroreflex function, and reduced the increase in water intake. In contrast to 2K1C rats, similar increases in MIF expression in the NTS of NT rats produced no changes in baseline MAP, baroreflex function, or water intake. CONCLUSIONS These results indicate that an increased expression of MIF within the NTS attenuates the development of hypertension and restores the baroreflex function in 2K1C rats. [ABSTRACT FROM AUTHOR]

Abstract: GABAA and GABAB receptors activation with agonists muscimol and baclofen, respectively in the lateral parabrachial nucleus (LPBN), induces water and hypertonic NaCl intake in rats. The purpose of this study was to examine the effects of previous injections of losartan (AT1 angiotensin receptor antagonist) into the LPBN on 0.3M NaCl and water intake induced by baclofen injected bilaterally in the same area in fluid replete rats and in rats treated with the diuretic furosemide combined with a low dose of the angiotensin-converting enzyme inhibitor captopril injected subcutaneously. Male Wistar rats with stainless steel cannulas implanted bilaterally into the LPBN were used. Bilateral injections of baclofen (0.5nmol/0.2μl, n =6) into the LPBN in fluid replete rats induced 0.3M NaCl intake (22.4±6.5 vs. saline: 0.1±0.1ml/210min) and water intake (14.2±4.0 vs. saline: 0.6±0.6ml/210min) and pre-treatment of the LPBN with losartan (50μg/0.2μl) reduced 0.3M NaCl intake (7.4±7.0ml/210min) and water intake (2.8±2.4ml/210min) induced by baclofen. In rats treated with furosemide+captopril, pre-treatment with losartan into the LPBN attenuated the increase in 0.3M NaCl intake (13.3±3.2 vs. saline+baclofen: 24.3±3.9ml/180min) and water intake (4.8±2.1 vs. saline+baclofen: 19.5±6.6ml/180min) produced by baclofen. We conclude that baclofen may produce a non-specific blockade of the inhibitory mechanisms of LPBN (deactivation of LPBN inhibitory mechanisms) and this blockade is facilitated by angiotensin II acting on AT1 receptors in the LPBN, which drives rats to ingest large amounts of water and hypertonic NaCl independent if rats are fluid depleted or normohydrated. [Copyright &y& Elsevier]

• Data have contradicted that thirst and sodium appetite are distinct motivations. • In dehydrated rats, for example, thirst is non-selective for pure water. • Sodium appetite can appear under selective intracellular-dehydration. • A single motivation with thirst first, and sodium appetite second, may solve this. • Homology with facilitatory and inhibitory mechanisms of marine teleosts is implied. The objective of the present work is to examine from a new perspective the existence of causal factors not predicted by the classical theory that thirst and sodium appetite are two distinct motivations. For example, we ask why water deprivation induces sodium appetite, thirst is not "water appetite", and intracellular dehydration potentially causes sodium appetite. Contrary to the classical theory, we suggest that thirst first, and sodium appetite second, designate a temporal sequence underlying the same motivation. The single motivation becomes an "intervenient variable" a concept borrowed from the literature, fully explained in the text, between causes of dehydration (extracellular, intracellular, or both together), and respective behavioral responses subserved by hindbrain-dependent inhibition (e.g., lateral parabrachial nucleus) and forebrain facilitation (e.g., angiotensin II). A corollary is homology between rat sodium appetite and marine teleost thirst-like motivation that we name "protodipsia". The homology argument rests on similarities between behavior (salty water intake) and respective neuroanatomical as well as functional mechanisms. Tetrapod origin in a marine environment provides additional support for the homology. The single motivation hypothesis is also consistent with ingestive behaviors in nature given similarities (e.g., thirst producing brackish water intake) between the behavior of the laboratory rat and wild animals, rodents included. The hypotheses of single motivation and homology might explain why hyperosmotic rats, or eventually any other hyperosmotic tetrapod, shows paradoxical signs of sodium appetite. They might also explain how ingestive behaviors determined by dehydration and subserved by hindbrain inhibitory mechanisms contributed to tetrapod transition from sea to land. [ABSTRACT FROM AUTHOR]

Angiotensin II (Ang II) acts on Ang II type 1 (AT1) receptors located in the organum vasculosum and subfornical organ (SFO) of the lamina terminalis as a main facilitatory mechanism of sodium appetite. The brain serotonin (5‐HT) system with soma located in the dorsal raphe nucleus (DRN) provides a main inhibitory mechanism. In the present study, we first investigated the existence of Ang II AT1 receptors in serotonergic DRN neurones. Then, we examined whether whole body sodium depletion affects the gene expression of the AT1a receptor subtype and the presumed functional significance of AT1 receptors. Using confocal microscopy, we found that tryptophan hydroxylase‐2 and serotonin neurones express AT1 receptors in the DRN. Immunofluorescence quantification showed a significant reduction in 5‐HT content but no change in AT1 receptor expression or AT1/5‐HT colocalisation in the DRN after sodium depletion. Whole body sodium depletion also significantly increased Agtr1a mRNA expression in the SFO and DRN. Oral treatment with the AT1 receptor antagonist losartan reversed the changes in Agtr1a expression in the SFO but not the DRN. Losartan injection into either the DRN or the mesencephalic aqueduct had no influence on sodium depletion‐induced 0.3 mol L‐1 NaCl intake. The results indicate the expression of Agtr1a mRNA in the DRN and SFO as a marker of sodium depletion. They also suggest that serotonergic DRN neurones are targets for Ang II. However, the function of their AT1 receptors remains elusive. [ABSTRACT FROM AUTHOR]

Abstract: Heart failure (HF) is a complex syndrome that involves changes in behavioral, neural and endocrine regulatory systems. Dietary salt restriction along with pharmacotherapy is considered an essential component in the effective management of symptomatic HF patients. However, it is well recognized that HF patients typically have great difficulty in restricting sodium intake. We hypothesized that under HF altered activity in systems that normally function to regulate body fluid and cardiovascular homeostasis could produce an increased preference for the taste of salt. Therefore, this study was conducted to evaluate the perceived palatability (defined as salt preference) of food with different concentrations of added salt in compensated chronically medicated HF patients and comparable control subjects. Healthy volunteers (n =25) and medicated, clinically stable HF patients (n =38, NYHA functional class II or III) were interviewed and given an evaluation to assess their preferences for different amounts of saltiness. Three salt concentrations (0.58, 0.82, and 1.16g/100g) of bean soup were presented to the subjects. Salt preference for each concentration was quantified using an adjective scale (unpleasant, fair or delicious). Healthy volunteers preferred the soup with medium salt concentration (p =0.042), HF patients disliked the low concentration (p <0.001) and preferred the high concentration of salted bean soup (p <0.001). When compared to healthy volunteers, HF patients demonstrated a significantly greater preference for the soup with a high salt concentration (p =0.038). It is concluded that medicated, compensated patients under chronic treatment for HF have an increased preference for salt. [Copyright &y& Elsevier]

Abstract: Previous studies using non-specific serotonergic agonists and antagonists have shown the importance of serotonergic inhibitory mechanisms in the lateral parabrachial nucleus (LPBN) for controlling sodium and water intake. In the present study, we investigated whether the serotonergic 5-HT1A receptor subtype in the LPBN participates in this control. Male Holtzman rats had cannulas implanted bilaterally into the LPBN. Bilateral injections of the 5-HT1A receptor agonist, 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT, 0.1, 1.25, and 2.5 μg/0.2 μl), into the LPBN enhanced 0.3 M NaCl and water intake of rats injected subcutaneously with the diuretic furosemide (10 mg/kg bw) and a low dose of the angiotensin-converting enzyme inhibitor, captopril (5 mg/kg bw). The increase in NaCl intake produced by 8-OH-DPAT injections was reduced in dose-related manner by pre-treating the LPBN with the selective 5-HT1A serotonergic antagonist, WAY-100635 (WAY, 1 and 2 μg/0.2 μl). In contrast, WAY did not affect water intake produced by 8-OH-DPAT. WAY-100635 injected alone into the LPBN had no effect on NaCl ingestion. Injections of 8-OH-DAPT (0.1 μg/0.2 μl) into the LPBN also increased 0.3 M NaCl intake induced by 24-h sodium depletion (furosemide, 20 mg/kg bw plus 24 h of sodium-free diet). Serotonin (5-HT, 20 μg/0.2 μl) injected alone or combined with 8-OH-DPAT into the LPBN reduced 24-h sodium depletion-induced 0.3 M NaCl intake. Therefore, the activation of serotonergic 5-HT1A receptors in the LPBN increases stimulated hypertonic NaCl and water intake, while 5-HT injections into the LPBN reduce NaCl intake and prevent the effects of serotonergic 5-HT1A receptor activation. [Copyright &y& Elsevier]