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Purpose: This study aimed to determine the effect of menthol ice application on thirst, dry mouth, mouth taste, and bad mouth odor in patients who underwent laparoscopic cholecystectomy in the postoperative period., Design: The study was conducted as a randomized controlled trial with an experimental design., Methods: The study sample consisted of 90 patients who underwent laparoscopic cholecystectomy and met the inclusion criteria. Patients were divided into three groups by randomization program. Patients in the menthol ice and ice popsicle (ice prepared with drinking water only) group were administered menthol ice/ice popsicle (10 mL) twice at 20 minutes intervals. Patients in the control group did not receive any intervention. Routine practices of the clinic were performed by the nurses of the general surgery clinic. Postoperative thirst intensity, severity of dry mouth, bad taste, and bad odor in the mouth were evaluated at 0, 20, and 40 minutes., Findings: No statistically significant difference was found between the sociodemographic and clinical characteristics of the patients in the control group, menthol ice group, and ice popsicle group (P > .05). A statistically significant difference was found between the 3 groups in terms of thirst intensity and severity of dry mouth at times at the 20th and 40th minutes after the application (P < .01). We found a statistically significant difference between the bad taste and bad odor sensation scores of the patients in the control and intervention groups at the 20th and 40th minutes after the application (P < .05)., Conclusions: The study concluded that menthol ice and ice popsicle application are effective strategies to reduce the intensity of thirst, severity of dry mouth, bad taste, and bad odor in postoperative patients., Competing Interests: Declaration of Competing Interest The authors declare no actual or potential conflict of interest., (Copyright © 2024. Published by Elsevier Inc.)

Objective: The aim of this study was to conduct a comprehensive evaluation of the rehydration efficacy of QSBYD and elucidate its potential underlying mechanism., Design: 38 participants were randomly assigned to receive either QSBYD or placebo before and after exercise and heat-induced dehydration. Hydration indicators were measured over time. Blood tests assessed cellular anaerobic respiration metabolites, serum inflammatory markers, and coagulation markers. Perceptual measures of thirst, fatigue, and muscular soreness were also taken., Results: QSBYD consumption resulted in lower urine volume (Control vs. QSBYD: 260.83 ± 167.99 ml vs. 187.78 ± 141.34 ml) and smaller decrease in percentage of nude body weight change from baseline (Control vs. QSBYD: -0.52 ± 0.89% vs. -0.07 ± 0.52%). Although no significant differences in urine specific gravity, QSBYD resulted in reduced urine volume at 120 min, suggesting improved fluid retention. Furthermore, QSBYD resulted in lower levels of IL-1β (Control vs. QSBYD: 2.40 ± 0.68 vs. 1.33 ± 0.66 pg/mL), suggesting QSBYD may provide benefits beyond hydration., Conclusion: Further investigation into the underlying mechanisms and long-term effects of QSBYD on hydration is warranted. QSBYD may be an effective alternative to commercial sports drinks in mitigating dehydration effects.

Aims: We aim to analyse the effect of menthol on thirst intensity and thirst comfort in surgical patients., Background: Menthol has achieved good results in quenching thirst in patients in intensive care units, but its safety and reliability in perioperative fasting patients are unknown., Design: A systematic review with meta-analysis of intervention studies was performed., Data Sources: We used Chinese and English databases from their dates of inception to May 2022. Literature was retrieved from PubMed, Web of Science, Cochrane Library, Embase, CINHAL, SinoMed, CNKI, Wanfang and VIP database., Review Methods: Two reviewers independently examined the records according to the eligibility criteria and extracted the data of each included study., Results: A total of seven studies were identified in this review, which included 537 surgical patients. Overall, menthol reduced thirst intensity in surgical patients and decreased thirst discomfort. Further subgroup analysis revealed that the menthol intervention significantly improved thirst intensity in surgical patients during preoperative and postoperative fasting periods. The Egger's tests showed no significant bias (p = 0.113 and 0.553, thirst intensity and thirst discomfort, respectively)., Conclusion: Menthol intervention effectively improved thirst intensity and thirst discomfort during fasting in surgical patients, but more large-scale, multicentre randomized controlled trials are required to confirm these findings further., (© 2023 The Authors. International Journal of Nursing Practice published by John Wiley & Sons Australia, Ltd.)

Thirst is a complex physiological compensatory mechanism but could also be associated with drugs. This association was poorly investigated previously. Using the WHO global pharmacovigilance database, Vigibase®, disproportionality analyses potential associations between exposure to drugs and thirst reports were performed. All reports of thirst in adults between 01/01/2000 and 31/12/2023 were included. Results are expressed as reporting odds ratio (ROR). Analysis of the 3186 reports of thirst (978 'serious') allowed, first, to confirm the association between thirst and exposure to vasopressin antagonists (tolvaptan), lithium, gliflozins (dapagliflozin, empagliflozin), pregabalin and antimuscarinic drugs (glycopyronium, oxybutynin, tiotropium). Second, new safety signals were described with monoamine reuptake inhibitors (antidepressants: duloxetine, venlafaxine; anti-obesity agent: sibutramine), antipsychotic (olanzapine), glucocorticoid (prednisolone), diuretic (furosemide) drugs as well with ribavirin or sodium oxybate. This study is the first to offer a list of drugs associated with thirst in humans., (© 2024 British Pharmacological Society.)

The current study compared mouth swills containing carbohydrate (CHO), menthol (MEN) or a combination (BOTH) on 40 km cycling time trial (TT) performance in the heat (32 °C, 40% humidity, 1000 W radiant load) and investigates associated physiological (rectal temperature (Trec), heart rate (HR)) and subjective measures (thermal comfort (TC), thermal sensation (TS), thirst, oral cooling (OC) and RPE (legs and lungs)). Eight recreationally trained male cyclists (32 ± 9 y; height: 180.9 ± 7.0 cm; weight: 76.3 ± 10.4 kg) completed familiarisation and three experimental trials, swilling either MEN, CHO or BOTH at 10 km intervals (5, 15, 25, 35 km). The 40 km TT performance did not differ significantly between conditions (F 2,14 = 0.343; p = 0.715; η 2 = 0.047), yet post-hoc testing indicated small differences between MEN and CHO (d = 0.225) and MEN and BOTH (d = 0.275). Subjective measures (TC, TS, RPE) were significantly affected by distance but showed no significant differences between solutions. Within-subject analysis found significant interactions between solution and location upon OC intensity (F 28,196 = 2.577; p < 0.001; η 2 = 0.269). While solutions containing MEN resulted in a greater sensation of OC, solutions containing CHO experienced small improvements in TT performance. Stimulation of central CHO pathways during self-paced cycling TT in the heat may be of more importance to performance than perceptual cooling interventions. However, no detrimental effects are seen when interventions are combined.

Background: Tolvaptan is a vasopressin type 2 receptor antagonist and has been used to treat autosomal dominant polycystic kidney disease (ADPKD) since 2014. There has been limited real-world data on the safety and efficacy of tolvaptan., Methods: This post-marketing surveillance was conducted to evaluate the long-term safety and the efficacy of tolvaptan in Japanese patients with ADPKD in real-world clinical settings. The baseline characteristics of 1630 patients treated with tolvaptan are reported. Safety analysis comprises evaluation of adverse drug reactions (ADRs). The efficacy evaluation includes percent change in total kidney volume (TKV) and change in estimated glomerular filtration rate (eGFR) before and after tolvaptan treatment., Results: Mean age was 49.7 ± 11.2 years and 843 (51.7%) patients were male. Baseline TKV was 2158 ± 1346 mL and eGFR was 44.4 ± 21.7 mL/min/1.73 m 2 . The majority of CKD patients were stage G3b (27.0%) and G4 (30.1%). Frequently reported ADRs were hepatic function abnormal (8.3%), thirst (8.2%), and hyperuricaemia (6.9%). The frequency of ALT elevation (> 30 and > 90 IU/L) was slightly high (32.9 and 8.3%) to previous studies. After tolvaptan treatment, the annual rate of percentage change in TKV reduced from 11.68%/year to 2.73%/year (P < 0.0001). Similar results were also obtained for the effect on change in eGFR from - 3.31 to - 2.28 mL/min/1.73 m 2 /year after initiation of tolvaptan treatment (P = 0.0403)., Conclusion: There were no major problems with safety of tolvaptan treatment and comparable efficacy for TKV and eGFR was observed in relation to the previous pivotal two randomized control trials in this post-marketing surveillance., (© 2021. The Author(s).)

Prolonged exercise in the heat elicits a number of physiological changes as glycogen stores are low and water and electrolytes are lost through sweat. However, it is unclear whether these changes provoke an increase in liking of saltiness and, therefore, palatability of an oral rehydration solution (ORS). Twenty-seven recreationally active participants ( n = 13 males; n = 14 females) completed sensory analysis of an ORS, a traditional sports drink (TS), and a flavored water placebo (PL) at rest and during 60 min (3 × 20-min bouts) of cycling exercise at 70% age-predicted maximum heart rate (HR max ) at 35.3 ± 1.4 °C and 41 ± 6% relative humidity. Before and after every 20 min of exercise, drinks were rated (using 20-mL beverage samples) based on liking of sweetness, liking of saltiness, thirst-quenching ability, and overall liking on a nine-point hedonic scale. Hydration status was assessed by changes in semi-nude body mass, saliva osmolality (S Osm ), and saliva total protein concentration (S PC ). After 60 min of exercise, participants lost 1.36 ± 0.39% (mean ± SD) of body mass and there were increases in S Osm and S PC. At all time points, liking of sweetness, saltiness, thirst-quenching ability, and overall liking was higher for the TS and PL compared to the ORS ( p < 0.05). However, the saltiness liking and thirst-quenching ability of the ORS increased after 60 min of exercise compared to before exercise ( p < 0.05). There was also a change in predictors of overall liking with pre-exercise ratings mostly determined by liking of sweetness, saltiness, and thirst-quenching ability ( p < 0.001), whereas only liking of saltiness predicted overall liking post-exercise (R 2 = 0.751; p < 0.001). There appears to be a hedonic shift during exercise in which the perception of saltiness becomes the most important predictor of overall liking. This finding supports the potential use of an ORS as a valuable means of hydration during the latter stages of prolonged and/or intense exercise in the heat.

Two recent studies challenged traditional paradigms of mammalian sodium physiology, suggesting that sodium reduction might cause weight gain by altering metabolism. This new theory has important implications for population-wide dietary recommendations. However, these observations have not been confirmed. In the DASH (Dietary Approaches to Stop Hypertension)-Sodium trial, 412 adults with systolic blood pressure of 120 to 159 mm Hg and diastolic blood pressure of 80 to 95 mm Hg not taking antihypertensive medications were randomly assigned to the DASH diet or a control diet (parallel design). On their assigned diet, participants randomly consumed each of the 3 sodium levels for 4 weeks (crossover design). Participants were provided all meals but could drink noncaloric beverages (eg, water) freely. Throughout the trial, energy intake was adjusted to maintain weight constant. The 3 sodium levels (at 2100 kcal/day) were: low (1150 mg of Na/day), medium (2300 mg of Na/day), and high (3450 mg of Na/day). Energy intake, weight, self-reported thirst, and 24-hour urine volume were assessed after each period. Participants were 57% women and 57% black; mean age was 48 years [SD, 10]). Among those assigned the control, mean weight increased slightly with higher sodium but not among those assigned DASH. Energy intake did not vary across sodium levels in either diet ( P -trends ≥0.36). Higher sodium resulted in more thirst ( P -trends <0.001 on both diets) and higher urine volume (suggesting higher fluid intake) during the control diet ( P -trend=0.007). Reducing sodium did not increase energy requirements to maintain stable weights but did decrease thirst and urine volume (control diet only), findings consistent with the traditional understanding of mammalian sodium physiology. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT00000608.

Aims and Objectives: To compare mentholated popsicle with usual care (absolute fasting) in the change of thirst intensity and discomfort of patients in the preoperative fasting., Background: Thirst is defined as the desire to drink water, and it is considered to be a multifactorial symptom. In the preoperative fasting, the patient may experience intense thirst, often for a long time, that can lead to feelings of suffocation, desperation, fear and anxiety., Design: A randomised controlled trial., Methods: Forty patients, aged between 18-60 years, were randomised to mentholated popsicle group or absolute fasting group (twenty in each). The primary outcomes were thirst intensity, evaluated by a numeric scale ranging from 0 (no thirst)-10 (the worst possible thirst), and discomfort from thirst (evaluated by the Perioperative Thirst Discomfort Scale), both measured twice (baseline and after 20 min of intervention). The CONSORT checklist was used to report this study., Results: Mean age was similar in both groups (38 years in the mentholated popsicle group and 39 in the absolute fasting group). At baseline, the mentholated popsicle group had higher median for the scales of intensity (6.5) and discomfort (7.5) from thirst than the absolute fasting group (5.0 and 5.0, respectively). At the end of 20 min, the popsicle group had a statistically significant decrease in intensity and discomfort from thirst (median decreases of 5.0 and 7.0 points, respectively) when compared to the absolute fasting group (median increases of 0.5 and 1.0 points, respectively)., Conclusions: The use of mentholated popsicle decreased the intensity and discomfort from thirst, and it is a viable strategy for the management of thirst in the preoperative fasting., Relevance to Clinical Practice: In the preoperative fasting, making mentholated popsicles available to patients is an easy strategy to manage thirst, which might lead to better care., (© 2019 John Wiley & Sons Ltd.)

In response to an increase in osmolarity or a decrease in plasma volume, surgical patients often experience thirst during the perioperative period. Thirst causes intense discomfort for patients, but perioperative nurses and health care providers have received minimal direction on how to address this concern. This article presents evidence related to the advances in the management of patients' thirst and discusses clinical strategies that perioperative personnel can safely implement for their patients during the preoperative and postoperative periods. The Thirst Study and Research Group at Londrina State University, Brazil, developed the Thirst Management Model to provide a standardized method for perioperative personnel. Four pillars comprise this model: identification of thirst, measurement of thirst, safety assessment for the management of thirst, and application of relief strategies. This evidence-based model should assist perioperative nurses with translating knowledge and scientific evidence into clinical practice to provide safe patient care., (© AORN, Inc, 2020.)

The aim of the present study was to determine whether the TRPV1 channel is involved in the onset of sodium appetite. For this purpose, we used TRPV1-knockout mice to investigate sodium depletion-induced drinking at different times (2/24 h) after furosemide administration combined with a low sodium diet (FURO-LSD). In sodium depleted wild type and TRPV1 KO (SD-WT/SD-TPRV1-KO) mice, we also evaluated the participation of other sodium sensors, such as TPRV4, Na X and angiotensin AT1-receptors (by RT-PCR), as well as investigating the pattern of neural activation shown by Fos immunoreactivity, in different nuclei involved in hydromineral regulation. TPRV1 SD-KO mice revealed an increased sodium preference, ingesting a higher hypertonic cocktail in comparison with SD-WT mice. Our results also showed in SD-WT animals that SFO-Trpv4 expression increased 2 h after FURO-LSD, compared to other groups, thus supporting a role of SFO-Trpv4 channels during the hyponatremic state. However, the SD-TPRV1-KO animals did not show this early increase, and maybe as a consequence drank more hypertonic cocktail. Regarding the SFO-Na X channel expression, in both genotypes our findings revealed a reduction 24 h after FURO-LSD. In addition, there was an increase in the OVLT-Na X expression of SD-WT 24 h after FURO-LSD, suggesting the participation of OVLT-Na X channels in the appearance of sodium appetite, possibly as an anticipatory response in order to limit sodium intake and to induce thirst. Our work demonstrates changes in the expression of different osmo‑sodium-sensitive channels at specific nuclei, related to the body sodium status in order to stimulate an adequate drinking., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Thirst has evolved for vertebrate terrestrial adaptation. We previously showed that buccal drying induced a series of drinking behaviours (migration to water-taking water into the mouth-swallowing) in the amphibious mudskipper goby, thereby discovering thirst in ray-finned fish. However, roles of dipsogenic/antidipsogenic hormones, which act on the thirst center in terrestrial tetrapods, have remained unclear in the mudskipper thirst. Here we examined the hormonal effects on the mudskipper drinking behaviours, particularly the antagonistic interaction between angiotensin II (AngII) and atrial natriuretic peptide (ANP) which is important for thirst regulation in mammalian 'forebrain'. Expectedly, intracerebroventricular injection of ANP in mudskippers reduced AngII-increased drinking rate. ANP also suppressed the neural activity at the 'hindbrain' region for the swallowing reflex, and the maintenance of buccopharyngeal water due to the swallowing inhibition may attenuate the motivation to move to water. Thus, the hormonal molecules involved in drinking regulation, as well as the influence of buccopharyngeal water, appear to be conserved in distantly related species to solve osmoregulatory problems, whereas hormonal control of thirst at the forebrain might have been acquired only in tetrapod lineage during evolution.

Objective: to evaluate the effectiveness of menthol chewing gum, in the relief of the intensity and discomfort of the surgical patient's thirst in the preoperative period., Method: a randomized controlled trial, with 102 patients in the preoperative period, randomized in a control group, with usual care, and an experimental group, which received menthol gum, which was the study treatment variable. The primary clinical outcome was the variation in thirst intensity, evaluated by the Numeral Verbal Scale, and the secondary, the variation of the discomfort of thirst, evaluated by the Perioperative Thirst Discomfort Scale. Mann-Whitney test was used to compare measures between groups. The significance level adopted was of 0.05., Results: menthol chewing gum significantly reduced the intensity (p <0.001), with Cohen's medium-effect d, and thirst discomfort (p <0.001), with a large-effect Cohen's d., Conclusion: menthol chewing gum was effective in reducing the intensity and discomfort of preoperative thirst. The strategy proved to be an innovative, feasible and safe option in the use for the surgical patient, in the management of the preoperative thirst, in elective surgeries. NCT: 03200197.

Objective: Acyl ghrelin, which is the endogenous ligand for the growth hormone secretagogue receptor, potently stimulates pituitary growth hormone release, and to some degree adrenocorticotropic hormone and prolactin. Ghrelin is also orexigenic and has recently been shown to stimulate renal sodium absorption in rodent models. Increased thirst sensation has been observed as a side effect of acyl ghrelin administration in some human studies. The objective of this clinical trial was to investigate the direct effects of acyl ghrelin on thirst sensation and sodium excretion in hypopituitary patients., Design: Hypopituitary patients on stable replacement with hydrocortisone and growth hormone were investigated in two double-blind and placebo-controlled crossover studies. The patients received a 5-h intravenous infusion of acyl ghrelin (5 pmol/kg/min in the first study and 1 pmol/kg/min in the second study). Thirst sensation was measured on a Visual Analog Scale (VAS). In the second study plasma osmolality, vasopressin, copeptin, water intake, diuresis and urinary excretion of sodium and creatinine were measured., Results: In the initial study, acyl ghrelin (5 pmol/kg/min) increased thirst sensation (time × treatment analysis of variance for the effect of acyl ghrelin infusion P = 0.003). In the second study acyl ghrelin (1 pmol/kg/min) also increased thirst (P = 0.04) but did not affect urinary excretion of either sodium or water., Conclusions: We demonstrate that acyl ghrelin infusion increases thirst sensation, without affecting sodium excretion or diuresis in human subjects.

Objective: To evaluate the effectiveness of the menthol package (lip hydration and ice popsicles) compared to a package of non-menthol measures (lip hydration and ice popsicles) as a way to relieve thirst in patients in the Anesthetic Recovery Room., Method: Randomized and parallel trial study, with 120 patients randomized patients in an experimental group - menthol measurements (n=59) and control group - measures without menthol (n = 61)., Results: There was a significant (p<0.05) decrease in intensity, hydration, dryness and taste in the oral cavity between the three moments of assessment/intervention in the two groups. The difference was significant in the experimental group for thirst intensity at the second assessment/intervention point (p<0.05) after a single administration of the menthol package., Conclusion: There was a reduction in thirst intensity in both groups. Patients who received menthol packages showed a significant decrease in intensity after a single evaluation/intervention time. NCT: 02869139.

Objective: To identify and analyze the evidence on the effect of chewing gum on thirst in adults., Method: Integrative review, guided by the question: "What is the scientific evidence about the effects of chewing gum on adult's thirst?" LILACS, PubMed, Scopus and Web of Science were the databases consulted., Results: Of a total of 2,414 articles found, 12 papers were selected whose publications varied between 1991 and 2016. The use of chewing gum resulted in increased salivary volume (five studies), xerostomia relief (seven studies), and thirst reduction (four studies). It was not possible to establish the number of chewing gums per day, being frequent the recommendation to use as desired. There was a predominance of studies with patients under dialysis and with cancer., Conclusion: Chewing gum is an effective strategy to reduce thirst discomfort in adults.

Most investigators use a single treatment such as water deprivation or dietary sodium deficiency to evaluate thirst or sodium appetite, which underlie behavioral responses to body fluid challenges. The goal of the present experiments was to assess the effects of combined treatments in driving behaviors. Therefore, we evaluated the effect of combined overnight water deprivation and dietary sodium deficiency on water intake and salt intake by adult male rats in 2-bottle (0.5M NaCl and water) tests. Overnight water deprivation alone increased water intake, and 10days of dietary sodium deficiency increased 0.5M NaCl intake, with a secondary increase in water intake. During combined water deprivation and dietary sodium deficiency, water intake was enhanced and 0.5M NaCl was reduced, but not eliminated, suggesting that physiologically relevant behavioral responses persist. Nonetheless, the pattern of fluid intake was altered by the combined treatments. We also assessed the effect of these behaviors on induced deficits in body sodium and fluid volume during combined treatments and found that, regardless of treatment, fluid ingestion partially repleted the induced deficits. Finally, we examined urine volume and sodium excretion during dietary sodium deficiency with or without overnight water deprivation and found that, whether or not rats were water deprived, and regardless of water consumption, sodium excretion was minimal. Thus, the combination of water deprivation and dietary sodium deficiency appears to arouse drives that stimulate compensatory behavioral responses. These behaviors, in conjunction with physiological adaptations to the treatments, underlie body sodium and volume repletion in the face of combined water deprivation and dietary sodium deficiency., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Thirst and sodium appetite are motivational states that lead to the search for and ingestion of water and sodium, thus contributing to maintenance of hydromineral balance. Oestrogens affect fluid intake and sodium preference. Bisphenol A (BPA) is an environmental endocrine-disrupting substance with oestrogenic activity. Whether there are sex differences in the ingestive effects of BPA is unknown. Therefore, the aim of the present work was to determine the effect of short-term treatment of low doses of BPA on thirst and sodium appetite in adult male and ovariectomised Wistar rats. Rats were subcutaneously injected with either vehicle or 10, 50, 100, or 500 μg/kg/day BPA for a week. Two-bottle tests (water and 2.7% NaCl solution) were conducted in the animals' home cages with and without 24 h water deprivation. BPA reduced water and 2.7% NaCl intakes in a sex-dependent-manner. Fluid intakes displayed inverted U-shaped dose-response curves, with different dose dependencies in spontaneously drinker rats than after 24 h water deprivation dehydration. Future studies on the role of BPA in sex-dependent body fluid homeostasis should elucidate the effects of BPA on the neuroendocrine controls of thirst and salt appetite., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

New Findings: What is the central question of this study? The central goal of this study was to understand the effects of central angiotensin-(1-7) on basal and osmotically stimulated water intake in rats. What is the main finding and its importance? This study demonstrated that central administration of angiotensin-(1-7) did not induce thirst in basal conditions but increased water intake after osmotic stimulation, such as water deprivation and salt loading. These results indicate a new function for this peptide, which, in turn, allows for future research on the mechanisms through which angiotensin-(1-7) influences osmotic thirst. Angiotensin-(1-7) [Ang-(1-7)] is generated by type 2 angiotensin-converting enzyme (ACE2) and binds to the MAS receptor. Although it is well known that Ang-(1-7) functionally antagonizes the effects of the classical renin-angiotensin system in several situations, the role of Ang-(1-7) in hydromineral homeostasis is not clear. The aim of this study was to assess the role of Ang-(1-7) on neuroendocrine responses to hyperosmolality in rats. Male Wistar rats were divided into the following three groups: control; 24 h of water deprivation (WD); and 24 h of salt loading (SL; 1.8% NaCl). Intracerebroventricular (i.c.v.) injections of Ang-(1-7) or vehicle were given to assess water intake and plasma concentration of vasopressin. Additionally, the brains from control and WD groups were collected to evaluate gene expression in the subfornical organ (SFO), paraventricular nucleus (PVN) and supraoptic nucleus (SON). It was found that i.c.v. Ang-(1-7) did not change water and salt intake in control rats; however, Ang-(1-7) increased water intake after WD and SL, with no change in salt intake. Plasma vasopressin was not changed by i.c.v. Ang-(1-7) in control or WD rats. Moreover, WD increased Mas gene expression in the SON and PVN, with no changes in Ace2 mRNA levels. In conclusion, Ang-(1-7) increases thirst after osmotic stimuli, indicating that a previous sensitization to its action is necessary. This finding is consistent with the increased Mas gene expression in the PVN and SON after water deprivation., (© 2017 The Authors. Experimental Physiology © 2017 The Physiological Society.)

The sensation of thirst plays an important role in the consumption of water or other fluids to rehydrate the body in order to keep bodily functions working properly. An increase in saliva secretion, wetting the mouth by ingestion of liquids, and cooling and sour components in products can alleviate this sensation already before absorption of fluids by the body. This study aimed to investigate the thirst-quenching ability of water-based products differing in temperature and texture (cold solids and cool liquids), flavour (flavoured and non-flavoured) and sugar content in two consecutive experiments. The first experiment tested four products of 10ml each (flavoured popsicles, flavoured beverages, ice cubes, and water). 45 healthy, thirsty participants (8 men and 37 women, mean age 25.7years SD±6.6) were randomly assigned to a flavour group representing the flavour of the popsicles and beverages: mint, lemon, raspberry. Each flavour group tasted all four products (popsicles, beverages, water, ice cubes) in four sessions on consecutive days. Participants rated their thirst and four attributes (flavour intensity, thirst-quenching, refreshing, saliva stimulating) during 3min of consumption on a 100mm VAS scale and ranked all four products on thirst-quenching ability at the end of the last session. The second experiment was performed similarly (n=61, 6 men and 55 women, mean age 23.5years SD±2.87), but used sugar-reduced popsicles to compare to the regular popsicles from the first experiment. In addition, saliva was collected before and after consumption. In the first experiment, cold solid (55.8±0.99) and flavoured (55.9±0.95) products were found to be more thirst-quenching than cool liquid (52.8±0.96) and non-flavoured products (52.8±0.96). The second experiment confirmed that saliva production increased upon consumption of these popsicles, with an increase of saliva weight from 1.7g SD ±0.15 before consumption to 2.0 SD ±0.22 after consumption. Sugar-reduced popsicles were similar in thirst-quenching ability compared to regular popsicles. Overall, cold, solid, flavoured products (such as popsicles) performed best in quenching thirst, and it appeared that sugar-reduction in these products to create healthier alternatives can be achieved without compromising on thirst-quenching abilities. These results can be useful for optimisation of products to alleviate thirst in daily life, as well as in clinical settings for patients where fluid restriction is needed., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Daily injections of angiotensin II (AngII) cause a progressive increase of water intake that resembles a classically ascribed non-associative sensitization. Consistent with the presumption that the observed increase in intake was sensitization, we hypothesized that it resulted from a pharmacological interaction between AngII and its receptor. To test this hypothesis, and remove the influence of drinking itself, we implemented a delay in water access after injection of AngII (icv) on four consecutive 'induction days,' and then measured intake on the next day ('test day') when rats were allowed to drink immediately after AngII. The delay in water access effectively reduced water intake on the four induction days, and rats with longer delays in access drank less on the test day than did rats allowed to drink immediately after AngII on the induction days. Additional experiments ruled out a role for a conditioned drinking response to the injection alone, and demonstrated a lack of conditioned appetition after pairing injections of AngII with water given by intragastric catheter. Taken together, these findings suggest that the increased drinking observed after daily injections of AngII is a conditioned appetition after repeated pairings of AngII and water intake. We further conclude that repeated stimulation of the AngII receptor alone is not sufficient to drive appetition., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Dietary fibre has been shown to increase subjective satiating ratings. However data from human trials has produced mixed results, possibly due to different types of fibre which have diverse physicochemical properties and gastrointestinal transit behaviour. The aim of study 1 was to investigate whether orange juice (OJ) with 5.5 g of added orange pomace fibre (OPF) was as satiating as whole orange (WO, chopped and blended to a puree/liquid) compared with OJ. Study 2 was to evaluate the dose-dependent satiating effect of OPF delivered in an orange-flavoured beverage. Both studies were randomized, controlled, double blind, cross over in design with 4 intervention arms in study 1 including OJ, OPF, WO, and water, and 3 arms in study 2: orange-flavoured beverage with low (2.5 g) and high (5.5 g) dose of OPF (LD-OPF and HD-OPF), and orange-flavoured beverage without fibre (Control). Volunteers were asked to response to 8 questions relating to hunger, fullness, desire to eat, thirst and discomfort by visual analogue scale (VAS) for each question. Differences were detected in least squares mean estimates of composite satiety scores and each individual question with statistical modelling to adjust for differences in baseline scores. Addition of 5.5 g OPF either to OJ or to orange-flavoured beverage significantly increased the composite satiety scores compared with OJ (P < 0.0001) or Control (P < 0.0001), and the effect was comparative to WO. LD-OPF showed some satiating effect (less desire to eat) compared with Control (P = 0.038), though less effective than HD-OPF (P = 0.043). In conclusion, the addition of OPF to OJ was as effective at increasing satiety as WO consumption compared with OJ; and there was a trend of dose-dependent effect of OPF on satiety compared with the control., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Objective: Enhanced recovery after surgery is increasingly desired nowadays, and preoperative nutrient intake may be beneficial for this purpose. In this study, we investigated whether the intake of preoperative carbohydrate with amino acid (ONS) solution can improve starvation status and lipid catabolism before the induction of anesthesia., Methods: This randomized, prospective clinical trial included 24 patients who were divided into two groups before surgery under general anesthesia: a control group, comprising patients who fasted after their last meal the day before surgery (permitted to drink only water), and an ONS group, comprising patients who consumed ONS solution 2 h before surgery. Biochemical markers, the respiratory quotient, and psychosomatic scores were assessed at the initiation of anesthesia., Results: Compared with the control group, the ONS group showed significantly lower serum free fatty acid levels [control group: 828 (729, 1004) µEq/L, ONS group: 479 (408, 610) µEq/L, P = 0.0002, median (25th, 75th percentile)] and total ketone bodies [control group: 119 (68, 440) µmol/L, ONS group: 40 [27, 64] µmol/L, P = 0.037]. In addition, analysis using the Visual Analog Scale showed higher preoperative scores for anxiety, hunger, and thirst for the control group, with no differences in any other measure of subjective well-being between groups., Conclusions: The results of this study suggest that preoperative ONS intake improves lipid catabolism and starvation status before the induction of anesthesia. Furthermore, it can provide better preoperative mental health compared with complete fasting.

The subfornical organ (SFO) plays a pivotal role in body fluid homeostasis through its ability to integrate neurohumoral signals and subsequently alter behavior, neuroendocrine function, and autonomic outflow. The purpose of the present study was to evaluate whether selective activation of SFO neurons using virally mediated expression of Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) stimulated thirst and salt appetite. Male C57BL/6 mice (12-15 wk) received an injection of rAAV2-CaMKII-HA-hM3D(Gq)-IRES-mCitrine targeted at the SFO. Two weeks later, acute injection of clozapine N-oxide (CNO) produced dose-dependent increases in water intake of mice with DREADD expression in the SFO. CNO also stimulated the ingestion of 0.3 M NaCl. Acute injection of CNO significantly increased the number of Fos-positive nuclei in the SFO of mice with robust DREADD expression. Furthermore, in vivo single-unit recordings demonstrate that CNO significantly increases the discharge frequency of both ANG II- and NaCl-responsive neurons. In vitro current-clamp recordings confirm that bath application of CNO produces a significant membrane depolarization and increase in action potential frequency. In a final set of experiments, chronic administration of CNO approximately doubled 24-h water intake without an effect on salt appetite. These findings demonstrate that DREADD-induced activation of SFO neurons stimulates thirst and that DREADDs are a useful tool to acutely or chronically manipulate neuronal circuits influencing body fluid homeostasis., (Copyright © 2016 the American Physiological Society.)

Water-homeostasis is a fundamental physiological process for terrestrial life. In vertebrates, thirst drives water intake, but the neuronal circuits that connect the physiology of water regulation with emotional context are poorly understood. Vasopressin (VP) is a prominent messenger in this circuit, as well as L-glutamate. We have investigated the role of a VP circuit and interaction between thirst and motivational behaviors evoked by life-threatening stimuli in rats. We demonstrate a direct pathway from hypothalamic paraventricular VP-expressing, glutamatergic magnocellular neurons to the medial division of lateral habenula (LHbM), a region containing GABAergic neurons. In vivo recording and juxtacellular labeling revealed that GABAergic neurons in the LHbM had locally branching axons, and received VP-positive axon terminal contacts on their dendrites. Water deprivation significantly reduced freezing and immobility behaviors evoked by innate fear and behavioral despair, respectively, accompanied by decreased Fos expression in the lateral habenula. Our results reveal a novel VP-expressing hypothalamus to the LHbM circuit that is likely to evoke GABA-mediated inhibition in the LHbM, which promotes escape behavior during stress coping.

Adropin, a recently described peptide hormone produced in the brain and liver, has been reported to have physiologically relevant actions on glucose homeostasis and lipogenesis, and to exert significant effect on endothelial function. We describe a central nervous system action of adropin to inhibit water drinking and identify a potential adropin receptor, the orphan G protein-coupled receptor, GPR19. Reduction in GPR19 mRNA levels in medial basal hypothalamus of male rats resulted in the loss of the inhibitory effect of adropin on water deprivation-induced thirst. The identification of a novel brain action of adropin and a candidate receptor for the peptide should extend and accelerate the study of the potential therapeutic value of adropin or its mimetics for the treatment of metabolic disorders., (Copyright © 2016 the American Physiological Society.)

Intragastric hypertonic NaCl that simulates the ingestion of osmotically active substances by food intake induces thirst, vasopressin and oxytocin release, diuresis and natriuresis. Reactive oxygen species (ROS) produced endogenously in central areas may act modulating autonomic and behavioral responses. In the present study, we investigated the effects of H2O2 injected centrally on water intake and renal responses induced by increasing plasma osmolality with intragastric (ig) administration of 2M NaCl (2 ml/rat). Male Holtzman rats (280-320 g) with stainless steel cannula implanted in the lateral ventricle (LV) were used. Injections of H2O2 (2.5 μmol/1 μl) into the LV reduced ig 2M NaCl-induced water intake (3.1 ± 0.7, vs. PBS: 8.6 ± 1.0 ml/60 min, p<0.05), natriuresis (769 ± 93, vs. PBS: 1158 ± 168 μEq/120 min, p<0.05) and diuresis (4.1 ± 0.5, vs. PBS: 5.0 ± 0.5 ml/120 min, p<0.05). Injections of H2O2 into the LV also decreased meal associated water intake (4.9 ± 1.5, vs. PBS: 11.0 ± 1.7 ml/120 min). However, H2O2 into the LV did not modify 2% sucrose intake (3.3 ± 1.5, vs. PBS: 5.4 ± 2.3 ml/120 min) or 24h food deprivation-induced food intake (8.2 ± 2.0, vs. PBS: 11.0 ± 1.6g/120 min), suggesting that this treatment does not produce nonspecific inhibition of ingestive behaviors. The data suggest an inhibitory role for H2O2 acting centrally on thirst and natriuresis induced by hyperosmolarity and on meal-associated thirst., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

The sensation of thirst experienced after heavy alcohol drinking is widely regarded as a consequence of ethanol (EtOH)-induced diuresis, but EtOH in high doses actually induces anti-diuresis. The present study was designed to investigate the introduction mechanism of water and salt intake after heavy alcohol drinking, focusing on action of acetaldehyde, a metabolite of EtOH and a toxic substance, using rats. The aldehyde dehydrogenase (ALDH) inhibitor cyanamide was used to mimic the effect of prolonged acetaldehyde exposure because acetaldehyde is quickly degraded by ALDH. Systemic administration of a high-dose of EtOH at 2.5 g/kg induced water and salt intake with anti-diuresis. Cyanamide enhanced the fluid intake following EtOH and acetaldehyde administration. Systemic administration of acetaldehyde with cyanamide suppressed blood pressure and increased plasma renin activity. Blockade of central angiotensin receptor AT1R suppressed the acetaldehyde-induced fluid intake and c-Fos expression in the circumventricular organs (CVOs), which form part of dipsogenic mechanism in the brain. In addition, central administration of acetaldehyde together with cyanamide selectively induced water but not salt intake without changes in blood pressure. In electrophysiological recordings from slice preparations, acetaldehyde specifically excited angiotensin-sensitive neurons in the CVO. These results suggest that acetaldehyde evokes the thirst sensation following heavy alcohol drinking, by two distinct and previously unsuspected mechanisms, independent of diuresis. First acetaldehyde indirectly activates AT1R in the dipsogenic centers via the peripheral renin-angiotensin system following the depressor response and induces both water and salt intake. Secondly acetaldehyde directly activates neurons in the dipsogenic centers and induces only water intake., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: Neurosarcoidosis is a rare and aggressive variant of systemic sarcoidosis which may result in hypothalamic-pituitary dysfunction. We report a case of hypothalamic hypopituitarism secondary to neurosarcoidosis complicated by adipsic diabetes insipidus (ADI). Initiation of anti-tumour necrosis factor-α (TNF-α) therapy resulted in both radiological disease remission and recovery of osmoregulated thirst appreciation after 3 months., Case Summary: A 22-year-old man was referred to the endocrinology service with profound weight gain, polyuria and lethargy. Biochemical testing confirmed anterior hypopituitarism while posterior pituitary failure was confirmed by hypotonic polyuria responding to desmopressin. Magnetic resonance imaging (MRI) demonstrated extensive hypothalamic infiltration; neurosarcoidosis was confirmed histologically after excisional cervical lymph node biopsy. Osmoregulated thirst appreciation was normal early in the disease course despite severe hypotonic polyuria. However, subsequent subjective loss of thirst appreciation and development of severe hypernatraemia in the setting of normal cognitive function indicated onset of ADI., Management: Clinical management involved daily weighing, regular plasma sodium measurement, fixed daily fluid intake and oral desmopressin. We initiated immunosuppressive therapy with pulsed intravenous anti-TNF-α therapy (infliximab) after multidisciplinary team consultation., Outcome: Infliximab therapy resulted in successful radiological disease remission and complete recovery of osmoregulated thirst appreciation. This was confirmed by subjective return of thirst response and maintenance of plasma sodium in the normal range in the absence of close biochemical monitoring., (© The Author 2013. Published by Oxford University Press on behalf of the Association of Physicians. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Little is known about steroidal control of thirst- and salt-appetite behaviors of mice. The current study investigates effects of fludrocortisone acetate (FCA), a steroid with potent glucocorticoid and mineralocorticoid effects, on thirst- and salt-appetite responses of C57BL/6 mice. Treatment with FCA produced dose-dependent (5, 10, and 25 mg/kg) increases in both magnitude and duration of water and sodium intake. Chronic elevation of water and saline intake was achieved with daily injections of FCA. Daily injection of FCA, when only 0.9% saline was available, produced a remarkably rapid increase in saline intake. A single injection of FCA stimulated brisk diuresis and natriuresis in fluid-restricted animals. This work is the first to demonstrate copious water drinking by mice in response to FCA. The results are discussed in terms of the possibility that the renal effects of FCA promote increases in water and sodium turnover and thereby, increases in water and sodium ingestion., (Copyright © 2015 the American Physiological Society.)

This work examined the effects of age on daily water and sodium ingestion and cardiovascular responses to chronic administration of the mineralocorticoid, aldosterone (ALDO) either alone or together with the glucocorticoid, dexamethasone (DEX). Young (4 mo), adult (12 mo), and aged (30 mo) male Brown Norway rats were prepared for continuous telemetry recording of blood pressure (BP) and heart rate (HR). Baseline water and sodium (i.e., 0.3 M NaCl) intake, BP, and HR were established for 10 days. Then ALDO (60 μg/day sc) was infused alone, or together with DEX (2.5 or 20 μg/day sc), for another 10 days. Compared with baseline levels, ALDO stimulated comparable increases in daily saline intake at all ages. ALDO together with the higher dose of DEX (i.e., ALDO/DEX20) increased daily saline intake more than did ALDO, but less so in aged rats. Infusion of ALDO/DEX20 increased mean arterial pressure (MAP), and decreased HR, more than did infusion of ALDO. The changes in MAP in response to both treatments depended on age. For all ages, MAP and saline intake increased simultaneously during ALDO, while MAP always increased before saline intake did during ALDO/DEX20. Contrary to our predictions, MAP did not increase more in old rats in response to either treatment. We speculate that age-related declines in cardiovascular responses to glucocorticoids contributed to the attenuated increases in sodium intake in response to glucocorticoids that were observed in older animals., (Copyright © 2015 the American Physiological Society.)

Cholinergic activation of the medial septal area (MSA) with carbachol produces thirst, natriuresis, antidiuresis and pressor response. In the brain, hydrogen peroxide (H2O2) modulates autonomic and behavioral responses. In the present study, we investigated the effects of the combination of carbachol and H2O2 injected into the MSA on water intake, renal excretion, cardiovascular responses and the activity of vasopressinergic and oxytocinergic neurons in the hypothalamic paraventricular (PVN) and supraoptic (SON) nuclei. Furthermore, the possible modulation of carbachol responses by H2O2 acting through K+ATP channels was also investigated. Male Holtzman rats (280-320 g) with stainless steel cannulas implanted in the MSA were used. The pre-treatment with H2O2 in the MSA reduced carbachol-induced thirst (7.9±1.0, vs. carbachol: 13.2±2.0 ml/60 min), antidiuresis (9.6±0.5, vs. carbachol: 7.0±0.8 ml/120 min,), natriuresis (385±36, vs. carbachol: 528±46 μEq/120 min) and pressor response (33±5, vs. carbachol: 47±3 mmHg). Combining H2O2 and carbachol into the MSA also reduced the number of vasopressinergic neurons expressing c-Fos in the PVN (46.4±11.2, vs. carbachol: 98.5±5.9 c-Fos/AVP cells) and oxytocinergic neurons expressing c-Fos in the PVN (38.5±16.1, vs. carbachol: 75.1±8.5 c-Fos/OT cells) and in the SON (57.8±10.2, vs. carbachol: 102.7±7.4 c-Fos/OT cells). Glibenclamide (K+ATP channel blocker) into the MSA partially reversed H2O2 inhibitory responses. These results suggest that H2O2 acting through K+ATP channels in the MSA attenuates responses induced by cholinergic activation in the same area., (Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.)

This study examined the effect of drinking and gargling on thirst perception (TP) in 33 young dehydrated female subjects (18-25 yrs), using the visual analogue scale (VAS). Group A subjects drank, while group B gargled the fluid provided - 0.0%, 0.9% and 1.8% NaCl (7.0 ml/kg body weight of fluid). The procedure was alternated two weeks later. All subjects dehydrated for 18 hours prior to the study, and the last 12-hour urine was collected and volume recorded. Subject who provided a 12 hr urine volume greater than 400 ml was excluded from the study. After recording the baseline TP, and voiding the bladder, drinking/gargling was done within 5 minutes, and the subsequent TPs were recorded at 5 minutes interval for 25 minutes. Blood samples were collected before and at the end of the 30 minutes, when urine volumes were recorded. Drinking (0.0% and 1.8% NaCl) resulted in an initial decrease in thirst perception, which was statistically significant (p<0.05) only up to 10 minutes. Water intake ad libitum (mean ± SEM) at the end of the 30 minutes was statistically significantly lower (p<0.05) only in the group that drank 0.0% NaCl. Gargling on the other hand did not affect TP and water intake throughout the period of study. It can be concluded that drinking, but not gargling reduces thirst perception irrespective of the tonicity of the fluid as earlier reported (Obika et. al., 2009; Salata et. al., 1987). This study suggests that the oropharyngeal receptors for TP are activated by recurrent stimulation by the act of drinking rather than gargling.

Background: There is increasing focus on providing high quality care for people at the end of life, irrespective of disease or cause, and in all settings. In the last ten years the use of care pathways to aid those treating patients at the end of life has become common worldwide. The use of the Liverpool Care Pathway in the UK has been criticised. In England the LCP was the subject of an independent review, commissioned by a Health Minister. The Neuberger Review acknowledged that the LCP was based on the sound ethical principles that provide the basis of good quality care for patients and families when implemented properly. It also found that the LCP often was not implemented properly, and had instead become a barrier to good care; it made over 40 recommendations, including education and training, research and development, access to specialist palliative care services, and the need to ensure care and compassion for all dying patients. In July 2013, the Department of Health released a statement that stated the use of the LCP should be "phased out over the next 6-12 months and replaced with an individual approach to end of life care for each patient".The impact of opioids was a particular concern because of their potential influence on consciousness, appetite and thirst in people near the end of life. There was concern that impaired patient consciousness may lead to an earlier death, and that effects of opioids on appetite and thirst may result in unnecessary suffering. This rapid review, commissioned by the National Institute for Health Research, used standard Cochrane methodology to examine adverse effects of morphine, fentanyl, oxycodone, and codeine in cancer pain studies as a close approximation to possible effects in the dying patient., Objectives: To determine the impact of opioid treatment on patient consciousness, appetite and thirst in randomised controlled trials of morphine, fentanyl, oxycodone or codeine for treating cancer pain., Search Methods: We assessed adverse event data reported in studies included in current Cochrane reviews of opioids for cancer pain: specifically morphine, fentanyl, oxycodone, and codeine., Selection Criteria: We included randomised studies using multiple doses of four opioid drugs (morphine, fentanyl, oxycodone, and codeine) in cancer pain. These were taken from four existing or ongoing Cochrane reviews. Participants were adults aged 18 and over. We included only full journal publication articles., Data Collection and Analysis: Two review authors independently extracted adverse event data, and examined issues of study quality. The primary outcomes sought were numbers of participants experiencing adverse events of reduced consciousness, appetite, and thirst. Secondary outcomes were possible surrogate measures of the primary outcomes: delirium, dizziness, hallucinations, mood change and somnolence relating to patient consciousness, and nausea, vomiting, constipation, diarrhoea, dyspepsia, dysphagia, anorexia, asthenia, dehydration, or dry mouth relating to appetite or thirst.Comparative measures of harm were known to be unlikely, and we therefore calculated the proportion of participants experiencing each of the adverse events of interest with each opioid, and for all four opioid drugs combined., Main Results: We included 77 studies with 5619 randomised participants. There was potential bias in most studies, with small size being the most common; individual treatment groups had fewer than 50 participants in 60 studies. Participants were relatively young, with mean age in the studies typically between 50 and 70 years. Multiple major problems with adverse event reporting were found, including failing to report adverse events in all participants who received medication, all adverse events experienced, how adverse events were collected, and not defining adverse event terminology or whether a reporting system was used.Direct measures of patient consciousness, patient appetite, or thirst were not apparent. For opioids used to treat cancer pain adverse event incidence rates were 25% for constipation, 23% for somnolence, 21% for nausea, 17% for dry mouth, and 13% for vomiting, anorexia, and dizziness. Asthenia, diarrhoea, insomnia, mood change, hallucinations and dehydration occurred at incidence rates of 5% and below., Authors' Conclusions: We found no direct evidence that opioids affected patient consciousness, appetite or thirst when used to treat cancer pain. However, somnolence, dry mouth, and anorexia were common adverse events in people with cancer pain treated with morphine, fentanyl, oxycodone, or codeine.We are aware that there is an important literature concerning the problems that exist with adverse event measurement, reporting, and attribution. Together with the known complications concerning concomitant medication, data collection and reporting, and nomenclature, this means that these adverse events cannot always be attributed unequivocally to the use of opioids, and so they provide only a broad picture of adverse events with opioids in cancer pain. The research agenda includes developing definitions for adverse events that have a spectrum of severity or importance, and the development of appropriate measurement tools for recording such events to aid clinical practice and clinical research.

Reproductive surgeries leave women more susceptible to postoperative hypervolemic hyponatremia because during this period women can retain water at an accelerated pace and much faster than they do sodium. This review proposes that estrogen and progestogen exposure play an important role in the increased risk of hyponatremia in menopausal women. Estrogen and progesterone exposure have important effects on both body fluid regulation and cardiovascular function and both of these reproductive hormones impact blood pressure responses to sodium loads. This article provides information on the effects of female reproductive hormones and hormone therapy (HT) on fluid regulation and cardiovascular function during menopause. Thirst- and fluid-regulating hormones respond to both osmotic and volume stimuli. Aging women maintain thirst sensitivity to osmotic stimuli but lose some thirst sensitivity to changes in central body fluid volume. Thus, older adults are more at risk of dehydration because they may replenish fluids at a slower rate. Estrogen therapy increases osmotic sensitivity for mechanisms to retain body water so may help menopausal women control body fluids and avoid dehydration. Some progestogens can mitigate estradiol effects on water and sodium retention through competition with aldosterone for the mineralocorticoid receptor and attenuating aldosterone-mediated sodium retention in the distal tubule. However, some progestogens can increase cardiovascular risks. Appropriate balance of these hormones within HT is important to avoid the negative consequences of body fluid and sodium retention, including edema and hypertension.

Depletion of extracellular fluids motivates many animals to seek out and ingest water and sodium. Animals with a history of extracellular dehydration display enhanced sodium appetite and, in some cases, thirst. The progressive increase in sodium intake induced by repeated sodium depletions is known as sensitization of sodium appetite. Administration of the diuretic and natriuretic drug, furosemide, along with a low dose of captopril (furo/cap), elicits thirst and a rapid onset of sodium appetite. In the present studies the furo/cap model was used to explore the physiological mechanisms of sensitization of sodium appetite. However, when thirst and sodium appetite were measured concurrently in the furo/cap model, individual rats exhibited sensitization of either thirst or sodium appetite. In subsequent studies, thirst and sodium appetite were dissociated by offering either water prior to sodium or sodium before water. When water and sodium intake were dissociated in time, the furo/cap model reliably produced sensitization of sodium appetite. It is likely that neuroplasticity mediates this sensitization. Glutamatergic N-methyl-d-aspartate receptor (NMDA-R) activation is critical for the development of most forms of neuroplasticity. Therefore, we hypothesized that integrity of NMDA-R function is necessary for the sensitization of sodium appetite. Pharmacological blockade of NMDA-Rs with systemic administration of MK-801 (0.15 mg/kg) prevented the sensitization of fluid intake in general when water and sodium were offered concurrently, and prevented sensitization of sodium intake specifically when water and sodium intake were dissociated. The involvement of NMDA-Rs provides support for the possibility that sensitization of sodium appetite is mediated by neuroplasticity.

Estradiol (E2) plays an important role in controlling the homeostasis of body fluids. Several studies have reported the involvement of the hypothalamic pituitary adrenal axis (HPA) in the homeostatic control of hydromineral balance and the influence of estrogens on the modulation of this system. Nevertheless, until now, the physiological relevance of HPA axis activity on the hydromineral balance in females has not yet been fully elucidated. Therefore, the objective of the present study was to evaluate the effects of E2 (20 μg/animal) pretreatment on neuroendocrine and hydroelectrolyte changes induced by adrenalectomy (ADX) with or without glucocorticoid hormone replacement (corticosterone, CORT; 10 mg/kg) in ovariectomized rats (OVX). The results show that sodium appetite, natriuresis and the elevated plasma angiotensin II (ANG II) concentration induced by ADX were attenuated by E2 pretreatment. Additionally, a reduction of AT1 mRNA expression in the subfornical organ (SFO) and an increase in plasma atrial natriuretic peptide (ANP) concentrations by E2 pretreatment were observed. E2 pretreatment reversed the reduction in water intake induced by ADX in ADX CORT-replaced rats. Moreover, E2 pretreatment attenuated corticotropin releasing factor (CRF) mRNA expression in the paraventricular nucleus (PVN) induced by ADX. In contrast, E2 pretreatment increased CRF mRNA expression in the PVN in ADX CORT-replaced rats. Taken together, these results suggest that E2 has an important role in the modulation of behavioral and neuroendocrine responses involved in the maintenance of body fluid homeostasis in ADX rats with or without glucocorticoid replacement therapy.

This study aims to determine the prevalence, types, and associated factors for the use of herbal remedies in hemodialysis patients. Two hundred participants were selected by stratified sampling and were systematically interviewed. One hundred and twenty-six patients (63%) had used herbal remedies some time since their initiation of dialysis treatment. The users of herbal remedies had a significantly older age than nonusers, but no other significant differences were observed. The most prevalent complaints that led to herbal remedies use were gastroenterological complaints, flushing, and excessive thirst. Cichorium intybus, Borage officinalis, Mentha longifolia, and Matricaria recutita were the most prevalently used herbs in our patients. More study should be done on safety and efficacy of these herbs for hemodialysis patients.

Purpose: The study evaluated whether the dual blockade of the renin-angiotensin system may influence the sodium balance in hemodialysis., Methods: The study involved 148 hemodialysis patients (male 85, female 63), mean age 59.6 ± 12.9 years. Participants were randomly selected to receive either angiotensin-converting enzyme inhibitor (ACEI)--subgroup A--or dual blockade ACEI and angiotensin receptor blocker (ARB)--subgroup AA., Results: At baseline, in the A versus AA subgroups, the pre-dialysis sodium concentrations (mmol/l) were 137.7 ± 0.5 versus 137.9 ± 0.8, the sodium gradients 2.6 ± 0.5 versus 2.9 ± 0.4, interdialytic weight gain (IWG) (kg) 3.1 ± 0.2 versus 3.0 ± 0.3, and thirst inventory score (points) 18.1 ± 1.0 versus 19.0 ± 1.7, respectively. After 3 months of therapy, a decrease in sodium concentration to 134.5 ± 0.5 and the increase of its gradient to 5.5 ± 0.5 were noted in the AA subgroup. An elevation of mean interdialytic weight gain to 3.47 ± 0.2 and thirst score to 21.3 ± 2.1 was observed. No significant changes in subgroup A were found. One month of the dialysate sodium concentration being lowered from 140 mmol/l to 138 mmol/l was associated with reduced serum sodium concentration and gradient, decreased IWG and restored moderate thirst score in the AA subgroup (137.5 ± 0.6 and 2.9 ± 0.6, 3.0 ± 0.5 and 19.2 ± 1.3, respectively)., Conclusions: The dual blockade of the renin-angiotensin system affects sodium balance, increasing the sodium gradient, thus elevating thirst sensation and enhancing interdialytic weight gain. In maintenance hemodialysis patients treated with both ACEI and ARB, lowered dialysate sodium levels should be prescribed.

Objective: Glucocorticoids seem to modify the release and effects of plasma arginine vasopressin (pAVP). However, underlying processes are not well understood. This study aimed to evaluate the mechanism of the modulating effects of glucocorticoids on pAVP and renal water reabsorption., Design: Fluid deprivation tests were performed without (d0) and after one (d1) and five days (d5) of oral prednisolone (Pred) pretreatment in a dosage relevant to drug therapy (30 mg/day)., Patients: Twelve healthy male volunteers participated in this trial., Measurements: Plasma and urinary osmolality, pAVP, renin, aldosterone, plasma atrial natriuretic peptide (ANP) as well as urinary secretion of aquaporin-2 (AQP2) and prostaglandin E(2) (PGE2) were analysed., Results: An appropriate rise in pAVP was observable during thirsting (P < 0.001), which was absent after Pred pretreatment. However, the plasma and urinary osmolality after Pred treatment did not differ when compared with the basal thirsting test. Unchanged urinary AQP2 excretion suggests AVP-independent mechanisms of renal fluid reabsorption. Plasma renin concentration as well as ANP was substantially increased after Pred intake at d1 and d5 (both P < 0.05), which may mediate such AVP-independent mechanisms. Urinary PGE2 secretion was not influenced by Pred pretreatment, making a PGE2-mediated effect on renal AQP2 translocation and water permeability unlikely. Increased efficacy of exogenous desmopressin at d1 and d5 indicates also a relative increase in AVP sensitivity of the tubular cells after Pred intake., Conclusions: The here presented data are compatible with an increased AVP sensitivity and a partially AVP-independent regulation of AQP2 translocation and renal fluid reabsorption during glucocorticoid treatment., (© 2012 Blackwell Publishing Ltd.)

The renin-angiotensin-aldosterone system makes a critical contribution to body fluid homeostasis, and abnormalities in this endocrine system have been implicated in certain forms of hypertension. The peptide hormone angiotensin II (AngII) regulates hydromineral homeostasis and blood pressure by acting on both peripheral and brain targets. In the brain, AngII binds to the angiotensin type 1 receptor (AT1R) to stimulate thirst, sodium appetite and both arginine vasopressin (AVP) and oxytocin (OT) secretion. The present study used an experimental model of endogenous AngII to examine the role of p44/42 mitogen-activated protein kinase (MAPK) as a signalling mechanism to mediate these responses. Animals were given a combined treatment of furosemide and a low dose of captopril (furo/cap), comprising a diuretic and an angiotensin-converting enzyme inhibitor, respectively, to elevate endogenous AngII levels in the brain. Furo/cap induced p44/42 MAPK activation in key brain areas that express AT1R, and this effect was reduced with either a centrally administered AT1R antagonist (irbesartan) or a p44/42 MAPK inhibitor (U0126). Additionally, furo/cap treatment elicited water and sodium intake, and irbesartan markedly reduced both of these behaviours. Central injection of U0126 markedly attenuated furo/cap-induced sodium intake but not water intake. Furthermore, p44/42 MAPK signalling was not necessary for either furo/cap- or exogenous AngII-induced AVP or OT release. Taken together, these results indicate that p44/42 MAPK is required for AngII-induced sodium appetite but not thirst or neurohypophysial secretion. This result may allow for the discovery of more specific downstream targets of p44/42 MAPK to curb sodium appetite, known to exacerbate hypertension, at the same time as leaving thirst and neurohypophysial hormone secretion undisturbed., (© 2012 British Society for Neuroendocrinology.)

Aging results in reduced water and sodium intake responses in male rats. Because sex differences exist for water and sodium ingestion of young adult animals, we hypothesized that these sex differences would protect against the diminished water and sodium ingestion of aged female rats. Water and sodium intakes were examined in male and female young adult and aged Brown Norway rats in response to dipsogenic stimuli. Aged rats of both sexes consumed less water than young adult rats in response to 24-h water deprivation, thermal dehydration and hypertonic NaCl injection, but not to peripheral angiotensin II. Aged females consumed more water than males in response to hypertonic NaCl injection. Following sodium depletion, intake of 0.5 M NaCl solution over 2 h was higher in young adult rats than in aged rats. Aged animals had reduced angiotensin receptor 1A (AT(1A)) and atrial natriuretic peptide (ANP) mRNA expression in hypothalamic tissue with no sex differences. These data indicate that female rats are not protected from water and sodium intake deficits that occur in aging and that sex differences in sodium intake in young adult rats are eliminated with aging., (Copyright © 2012 Elsevier Inc. All rights reserved.)

During heat waves many elderly individuals die as a consequence of dehydration. This is partially due to deficits in mechanisms controlling thirst. Reduced thirst following dipsogenic stimuli is well documented in aged humans and rodents. Low in vivo long-chain omega-3 fatty acid levels, as can occur in aging, have been shown to alter body fluid and sodium homeostasis. Therefore, the effect of dietary omega-3 fatty acid supplementation on drinking responses in aged rats was examined. Omega-3 fatty acids reversed thirst deficits in aged rats following dehydration and hypertonic stimuli; angiotensin (ANG) II induced drinking was unaffected in aged rats. Plasma atrial natriuretic peptide (ANP) and arginine vasopressin (AVP) were altered with age, but not affected by diet. Aged omega-3 fatty acid deficient animals displayed increased hypothalamic cytosolic phospholipase A(2) (cPLA(2)), cyclooxygenase (COX)-2, and prostaglandin E (PGE) synthase messenger (m)RNA expression, compared with animals that received omega-3 fatty acids. The aged low omega-3 fatty acid fed animals had significantly elevated hypothalamic PGE(2) compared with all other groups. Hypothalamic PGE(2) was negatively correlated with drinking induced by both dehydration and hypertonicity. The results indicate that PGE(2) may be the underlying mechanism of the reduced thirst observed in aging., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Nesfatin-1, a post-translational product of the nucleobindin-2 (NucB2) gene, is produced in several brain areas known to be important in neuroendocrine, autonomic and metabolic function, including the hypothalamus and medulla. The hallmark action of the peptide is its ability at picomole doses to inhibit food and water intake in rodents and, indeed, the effect on water intake is more pronounced than that on food intake. In preliminary studies, we observed a decrease in hypothalamic NucB2 expression in response to overnight water deprivation even when food was present, which reversed when water was returned to the animals. We therefore hypothesised that the effect of nesfatin-1 on water drinking was independent of its anorexigenic action. Indeed, rats administered nesfatin-1 i.c.v. consumed significantly less water than controls in response to a subsequent, dipsogenic dose of angiotensin II, or upon return of water bottles after 18 h of fluid restriction (food present), or in response to a hypertonic challenge. Pretreatment with an antisense oligonucleotide against nesfatin-1 significantly reduced levels of immunoreactive nesfatin-1 in the hypothalamic paraventricular nucleus and resulted in exaggerated drinking responses to angiotensin II. The results obtained in the present study suggest that locally produced nesfatin-1 may be an important component of the hypothalamic mechanisms controlling fluid and electrolyte homeostasis., (© 2012 The Authors. Journal of Neuroendocrinology © 2012 Blackwell Publishing Ltd.)

Objective: Cevimeline and pilocarpine (muscarinic receptor agonists) are used as sialogogues in xerostomia treatment. It is important to know the different effects on their salivary mechanisms and the side effects. The aim of the present study was to clarify and compare the comprehensive effects of cevimeline to pilocarpine on salivary, cardiovascular and central mechanisms in rats., Design: Under anaesthesia, whole saliva secretion, parotid blood flow and blood pressure were measured following intra-peritoneal administrations of the sialogogues. In digested parotid cells, intracellular Ca(2+) concentrations were measured after the sialogogue application. In the conscious condition, changes in angiotensin II-induced water intake were observed after cevimeline administration. In the subfornical organ, which is a thirst-related central nucleus, the effect of cevimeline on the neuronal activity was electrophysiologically investigated., Results: Cevimeline at 80μmolkg(-1) showed slowly increasing and lasting salivation, a similar blood flow increment in the parotid gland and higher pressor response when compared to pilocarpine at 4μmolkg(-1). In parotid cells, cevimeline increased the intracellular Ca(2+) concentration in a similar manner to pilocarpine, but at a higher concentration than pilocarpine. Cevimeline inhibited angiotensin II-induced water intake and neuronal activity in the subfornical organ, which is in contrast to reported effects of pilocarpine., Conclusions: Cevimeline activates common salivary mechanism with pilocarpine but has a slower onset of activation, longer duration of salivation and an increased pressor response at higher doses. The anti-dipsogenic effect of cevimeline is due to the inhibitory neuronal effect on the thirst-related central nuclei., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

The effect of salt intensity on ad libitum intake of tomato soup was investigated when soup was served as a first course and as a second course. Also the effect of salt intensity in soup on subsequent sweet vs. savory choice of sandwich fillings was investigated. Forty-three healthy subjects consumed ad libitum a low-salt (LS), ideal-salt (IS) and high-salt (HS) tomato soup in both meal settings. The salt concentrations were selected on an individual basis, in a way that IS was most pleasant and LS and HS were similar in pleasantness. The ad libitum intake of IS soup was higher than that of LS and HS soup, and the ad libitum intake of LS soup was higher than that of HS soup. The meal setting, soup as a first or as a second course, did not affect ad libitum intake. Salt intensity in soup did not predict sweet vs. savory choice of fillings in grams or energy, although most sodium from fillings was consumed after intake of HS soup. In conclusion, a higher salt intensity lead to lower ad libitum intake of soup similar in palatability (LS vs. HS). In addition, salt intensity in soup does not predict sweet vs. savory food choice., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Previous studies have shown that (5-{4-[3-(R)-2-methylpyrrolin-1-yl-propoxy]phenyl}-2H-pyridazin-3-one) 2 had high affinity for both the human (hH(3)R K(i) = 2.8 nM) and rat H(3)Rs (rH(3)R K(i) = 8.5 nM) but displayed low oral bioavailability in the rat. Optimization of the 5-pyridazin-3-one R(2) and R(6) positions to improve the pharmacokinetic properties over 2 led to the identification of 5-{4-[3-(R)-2-methylpyrrolidin-1-yl)propoxy]phenyl}-2-pyridin-2-yl-2H-pyridazin-3-one 29. Compound 29 displayed high affinity for both human and rat H(3)Rs (hH(3)R K(i) = 1.7 nM, rH(3)R K(i) = 3.7 nM) with a greater than 1000-fold selectivity over the other histamine receptor subtypes and favorable pharmacokinetic properties across species (F = 78% rat, 92% dog, 96% monkey). It showed low binding to human plasma proteins, weakly inhibited cytochrome P450 isoforms, and displayed an excellent safety profile for a CNS-active compound. 29 displayed potent H(3)R antagonist activity in the brain in a rat dipsogenia model and demonstrated enhancement of cognitive function in a rat social recognition model at low doses. However, the development of compound 29 was discontinued because of genotoxicity.