Thirst Responses Research Articles

6520 Stimulated Copeptin Measurement in the Evaluation of a Patient Presenting Hypernatremia and Adipsia

Abstract Disclosure: B.R. Assunção: None. M.M. Freire: None. M. De Castro: None. A.C. Moreira: None. P.C. Elias: None. Introduction: Hypernatremia (hyperNA) in patients submitted to neurosurgery involving the hypothalamic region prompts the diagnosis of vasopressin deficiency (AVP-D), typically accompanied by increased thirst, polydipsia and polyuria. Classic adipsic AVP-D is characterized by hypotonic polyuria and no thirst in response to hyperNA. Clinical Case: A 21 yo male patient, followed since he had a surgery for a pilocytic astrocytoma of the third ventricle at 12 yo, presented hyperNA (154 mEq/L) with mild dehydration. He denied increased thirst, polyuria or polydipsia. Further evaluation showed elevated plasma and urinary osmolalities (pOsm: 317 mOsm/Kg; uOsm: 878 mOsm/Kg). The patient was admitted for hydration and fluid balance. Oral water intake (2500-3000L/day) was prescribed. Serum sodium (Na+) decreased from 158 to 133 mEq/L within 72h, and no polyuria was detected at hyper or normonatremic states. A 3% saline infusion test (SIT) was performed with thirst visual scale and plasma copeptin (CP) assessment. Na+ rose from 139 to 150 mEq/L and pOsm from 295 to 321 mOsm/kg, with no rise in thirst scale (4,2 to 4,8 cm). Basal and maximal 3% SIT CP levels were 3.1 and 3.2 pmol/L, respectively, also displaying subnormal values. CP assessed under hypovolemic hyperNA (Na+: 158 mEq/L) was 4.1 pmol/L, suggesting that this patient might have an adispic disorder with subnormal thirst and AVP osmotic responses, explaining the lack of polyuria. Patient was treated with fixed daily fluid intake with a last follow-up Na+ of 141 mEq/L.Discussion: Adipsic AVP-D is characterized by hypotonic polyuria and no thirst in response to hyperNA. However, polyuria, a hallmark of clinical presentation, was not observed in the present case. Other adipsic disorders include upward resetting of the osmotic thresholds for both thirst and AVP release (Type A); sub-normal thirst and AVP responses to osmotic stimuli (Type B); and intact osmoregulation of AVP release with absent thirst response (Type D). The lack of polyuria even in normovolemic conditions and the subnormal thirst and CP responses to normovolemic hyperNA and dehydrate states suggest the present case to be a Type B adipsic disorder. In those patients, the secretion of small amounts of AVP in response to osmotic stimulation explains why they retain the ability to concentrate urine, limiting free water excretion. Treatment is based on a fixed fluid intake of around 2 liters per day. Conclusions: Adipsic AVP-D and other adipsic disorders are extremely rare, presenting a great challenge in the diagnosis and management. To our knowledge, this is the first description of CP assessment in a patient with hyperNA and adipsia. CP might be an important diagnostic approach to adipsic disorders. Presentation: 6/2/2024

Cannabinoids regulate an insula circuit controlling water intake

The insular cortex, or insula, is a large brain region involved in the detection of thirst and the regulation of water intake. However, our understanding of the topographical, circuit, and molecular mechanisms for controlling water intake within the insula remains parcellated. We found that type-1 cannabinoid (CB1) receptors in the insular cortex cells participate in the regulation of water intake and deconstructed the circuit mechanisms of this control. Topographically, we revealed that the activity of excitatory neurons in both the anterior insula (aIC) and posterior insula (pIC) increases in response to water intake, yet only the specific removal of CB1 receptors in the pIC decreases water intake. Interestingly, we found that CB1 receptors are highly expressed in insula projections to the basolateral amygdala (BLA), while undetectable in the neighboring central part of the amygdala. Thus, we recorded the neurons of the aIC or pIC targeting the BLA (aIC-BLA and pIC-BLA) and found that they decreased their activity upon water drinking. Additionally, chemogenetic activation of pIC-BLA projection neurons decreased water intake. Finally, we uncovered CB1-dependent short-term synaptic plasticity (depolarization-induced suppression of excitation [DSE]) selectively in pIC-BLA, compared with aIC-BLA synapses. Altogether, our results support a model where CB1 receptor signaling promotes water intake by inhibiting the pIC-BLA pathway, thereby contributing to the fine top-down control of thirst responses.

Hyponatremia due to preserved non-osmotic arginine vasopressin secretion in adipsic diabetes insipidus: a case report with review of literature.

Adipsic diabetes insipidus (ADI) is characterized by central diabetes insipidus and an impaired thirst response to hyperosmolality, leading to hypernatremia. Hyponatremia observed in patients with ADI has been considered a complication of desmopressin therapy. Herein, we present a case of impaired thirst sensation and arginine vasopressin (AVP) secretion without desmopressin therapy, in which hyponatremia developed due to preserved non-osmotic AVP secretion. A 53-year-old woman with hypopituitarism, receiving hydrocortisone and levothyroxine, experienced hyponatremia three times over 5 months without desmopressin treatment. The first hyponatremic episode (120 mEq/L) was complicated by a urinary tract infection with a plasma AVP level of 33.8 pg/mL. Subsequent hyponatremia episodes occurred after administration of antipsychotic (124 mEq/L) and spontaneously (125 mEq/L) with unsuppressed plasma AVP levels (1.3 and 1.8 pg/mL, respectively). Hypertonic saline infusion did not affect AVP or copeptin levels. Regulating water intake using a sliding scale based on body weight prevented the recurrence of hyponatremia without the use of desmopressin. Except during infection, plasma AVP levels (1.3 ± 0.4 pg/mL) were not significantly correlated with serum sodium levels (rs = -0.04, p = 0.85). In conclusion, we present a unique case of impaired thirst sensation and AVP secretion in which hyponatremia developed without desmopressin therapy. Preserved non-osmotic AVP secretion, possibly stimulated by glucocorticoid deficiency, may contribute to the development of hyponatremia in patients with ADI.

WNK1 promotes water homeostasis by acting as a central osmolality sensor for arginine vasopressin release.

Maintaining internal osmolality constancy is essential for life. Release of arginine vasopressin (AVP) in response to hyperosmolality is critical. Current hypotheses for osmolality sensors in circumventricular organs (CVOs) of the brain focus on mechanosensitive membrane proteins. The present study demonstrated that intracellular protein kinase WNK1 was involved. Focusing on vascular-organ-of-lamina-terminalis (OVLT) nuclei, we showed that WNK1 kinase was activated by water restriction. Neuron-specific conditional KO (cKO) of Wnk1 caused polyuria with decreased urine osmolality that persisted in water restriction and blunted water restriction-induced AVP release. Wnk1 cKO also blunted mannitol-induced AVP release but had no effect on osmotic thirst response. The role of WNK1 in the osmosensory neurons in CVOs was supported by neuronal pathway tracing. Hyperosmolality-induced increases in action potential firing in OVLT neurons was blunted by Wnk1 deletion or pharmacological WNK inhibitors. Knockdown of Kv3.1 channel in OVLT by shRNA reproduced the phenotypes. Thus, WNK1 in osmosensory neurons in CVOs detects extracellular hypertonicity and mediates the increase in AVP release by activating Kv3.1 and increasing action potential firing from osmosensory neurons.

Abstract #1404147: Adipsic Diabetes Insipidus in a Patient with Aggressive Suprasellar Mature Teratoma

Diabetes insipidus (DI) can be life-threatening if not properly diagnosed and managed. There are many etiologies of central diabetes insipidus including neoplasm, vascular disease, trauma, autoimmune disease, infection, granulomatous disease, drugs, and genetic disease. This report presents a patient who developed adipsic DI secondary to a rare etiology, a suprasellar mature teratoma. A 37-year-old man with no significant past medical history presented to the hospital for worsening altered mental status (AMS) for 5 months, headaches, and polydipsia. Hypernatremia with a sodium level of 175 was noted. Magnetic resonance imaging (MRI) of the brain showed a large, heterogenous, mixed solid cystic suprasellar mass measuring 3.4 x 2.6 x 2.7 cm invading the suprasellar structures and extending to the third ventricle with mass effect on the hypothalamus, thalami, and optic chiasm. Panhypopituitarism with DI, hypothyroidism, adrenal insufficiency, and hypogonadism was diagnosed. Open craniotomy for surgical resection of the mass was performed. Pathology revealed endodermal tissues representing small and large intestine and stratified keratinizing and nonkeratinizing squamous epithelium in a background of hemorrhage, fibrosis, chronic inflammation, and mucin consistent with a suprasellar mature teratoma. He was discharged on desmopressin 1 mcg subcutaneously twice daily, hydrocortisone, and levothyroxine. He presented 7 months later for AMS and severe hypernatremia on desmopressin 6 mcg subcutaneously twice daily. There was regrowth of the suprasellar mass with interval worsening in size (3.5 x 3.7 x 3.1 cm) and increased mass effect on the left internal carotid artery, anterior communicating artery, and third ventricle. Subsequently, he underwent endoscopic cyst fenestration and ventriculoperitoneal shunt placement. Panhypopituitarism persisted, and he remained obtunded. He was hospitalized for 2 months, and repeat MRI of the brain showed an interval increase in the size of the mass (4.7 x 3.6 x 3.3 cm) with surrounding vasogenic edema and mass effect on the optic chiasm, hypothalamus, and third ventricle concerning for right ventricular entrapment. Due to the aggressive nature of the tumor, it was deemed inoperable and the patient underwent comfort care measures. Suprasellar mature teratomas are rare tumors which respond to surgical resection with a 10-year survival rate of 93%. Hypothalamic damage from these tumors can lead to an inability to maintain thirst response which can be dangerous in central DI as severe hypernatremia can develop. In these patients, it is vital to evaluate for other pituitary hormone deficiencies.

Heatstroke risk informing system using wearable perspiration ratemeter on users undergoing physical exercise

We constructed an informing system to users for the heatstroke risk using a wearable perspiration ratemeter and the users’ thirst responses. The sweating ratemeter was constructed with a capacitive humidity sensor in the ventilated capsule. The timing point for informing heatstroke risk was decided to change from positive to negative on the second derivative of sweating curve. In addition, a wearable self-identification and -information system of thirst response was constructed with a smartphone. To evaluate the validity of wearable apparatus, we aimed to conduct human experiments of 16 healthy subjects with the step up and down physical exercises. The blood and urine samples of the subjects were collected before and after the 30-min physical exercise. The concentrations of TP, Alb, and RBC increased slightly with the exercise. In contrast, the concentrations of vasopressin in all subjects remarkably increased with the exercise. In almost subjects, they identified their thirst response until several min after the informing for heatstroke risk. In conclusion, the wearable ratemeter and self-information system of thirst response were suitable for informing system of heatstroke risk. The validity of timing point for informing heatstroke risk was confirmed with changes in the thirst response and concentrations of vasopressin in blood.

Human thirst behavior requires transformation of sensory inputs by intrinsic brain networks

BackgroundTo survive and thrive, many animals, including humans, have evolved goal-directed behaviors that can respond to specific physiological needs. An example is thirst, where the physiological need to maintain water balance drives the behavioral basic instinct to drink. Determining the neural basis of such behaviors, including thirst response, can provide insights into the way brain-wide systems transform sensory inputs into behavioral outputs. However, the neural basis underlying this spontaneous behavior remains unclear. Here, we provide a model of the neural basis of human thirst behavior.ResultsWe used fMRI, coupled with functional connectivity analysis and serial-multiple mediation analysis, we found that the physiological need for water is first detected by the median preoptic nucleus (MnPO), which then regulates the intention of drinking via serial large-scale spontaneous thought-related intrinsic network interactions that include the default mode network, salience network, and frontal-parietal control network.ConclusionsOur study demonstrates that the transformation in humans of sensory inputs for a single physiological need, such as to maintain water balance, requires large-scale intrinsic brain networks to transform this input into a spontaneous human behavioral response.

Water intake, thirst, and copeptin responses to two dehydrating stimuli in lean men and men with obesity.

Physiological systems responsible for water homeostasis and energy metabolism are interconnected. This study hypothesized altered responses to dehydration including thirst, ad libitum water intake, and copeptin in men with obesity. Forty-two men (22 lean and 20 with obesity) were stimulated by a 2-hour hypertonic saline infusion and a 24-hour water deprivation. In each dehydrating condition, thirst, ad libitum water intake after dehydration, and urinary and hormonal responses including copeptin were assessed. After each dehydration condition, ad libitum water intake was similar between both groups (p > 0.05); however, those with obesity reported feeling less thirsty (p < 0.05) and had decreased copeptin response and higher urinary sodium concentrations when stressed (p < 0.05). Angiotensin II, aldosterone, atrial and brain natriuretic peptides, and apelin concentrations did not differ by adiposity group and did not explain the different thirst or copeptin responses in men with obesity. However, leptin was associated with copeptin response in lean individuals during the hypertonic saline infusion (p < 0.05), but the relationship was diminished in those with obesity. Diminished thirst and copeptin responses are part of the obesity phenotype and may be influenced by leptin. Adiposity may impact pathways regulating thirst and vasopressin release, warranting further investigation.

Role of Yogurt in Children having Diarrhea and Severe Acute Malnutrition at Nutrition Stabilization Center Hyderabad

Aim: The aim of conducting this study is to evaluate the role of yogurt in the dietary management of diarrhea in the severe malnutriated children.&#x0D; Study Design: Observational prospective study.&#x0D; Place and Duration: Nutrition Stabilization Center, Department of Pediatrics Civil Hospital Hyderabad from 1st July 2018 to 31st December 2018.&#x0D; Methodology: A total of 100 children with severe acute malnutrition and Diarrhea, age 6 months to 5 years were enrolled. After admitting children were treated with yogurt instead of fluids, f-75 and ORS. Within 7 days of admission we observed and recorded that children tolerated the breast milk and yogurt, clinically improvement, General condition, Edema, Sunken eyes, Thirst, Skin pinch, Weight gain and Social response of baby. Chi-square test was also applied to observe the difference efficacy of yogurt in diarrhea in children suffering from malnutrition. P-value ≤0.05 was considered as significant.&#x0D; Results: Most of the children were 13 to 48 months of age. The average age and weight of the children was 32.04±13.53 months and 5.23±1.39kg respectively. Average number of stool was significantly reduced at day 1 and day 5. Overall it was observed that efficacy of yogurt in diarrhea in children suffering from malnutrition was 69%.&#x0D; Conclusion: This study suggest that yogurt-based diet is effective in treating diarrhea in severely acute malnourished children. It should be granted priority in the nutritional management of severe malnutriated children affected by diarrhea.

Hyponatraemia and hypernatraemia: Disorders of Water Balance in Neurosurgery.

Disorders of tonicity, hyponatraemia and hypernatraemia, are common in neurosurgical patients. Tonicity is sensed by the circumventricular organs while the volume state is sensed by the kidney and peripheral baroreceptors; these two signals are integrated in the hypothalamus. Volume is maintained through the renin-angiotensin-aldosterone axis, while tonicity is defended by arginine vasopressin (antidiuretic hormone) and the thirst response. Edelman found that plasma sodium is dependent on the exchangeable sodium, potassium and free-water in the body. Thus, changes in tonicity must be due to disproportionate flux of these species in and out of the body. Sodium concentration may be measured by flame photometry and indirect, or direct, ion-sensitive electrodes. Only the latter method is not affected by changes in plasma composition. Classification of hyponatraemia by the volume state is imprecise. We compare the tonicity of the urine, given by the sodium potassium sum, to that of the plasma to determine the renal response to the dysnatraemia. We may then assess the activity of the renin-angiotensin-aldosterone axis using urinary sodium and fractional excretion of sodium, urate or urea. Together, with clinical context, these help us determine the aetiology of the dysnatraemia. Symptomatic individuals and those with intracranial catastrophes require prompt treatment and vigilant monitoring. Otherwise, in the absence of hypovolaemia, free-water restriction and correction of any reversible causes should be the mainstay of treatment for hyponatraemia. Hypernatraemia should be corrected with free-water, and concurrent disorders of volume should be addressed. Monitoring for overcorrection of hyponatraemia is necessary to avoid osmotic demyelination.

Chapter 19 - Adipsic diabetes insipidus

Adipsic diabetes insipidus (ADI) is a rare but devastating disorder of water balance with significant associated morbidity and mortality. Most patients develop the disease as a result of hypothalamic destruction from a variety of underlying etiologies. Damage to osmolar-responsive neuroreceptors, primarily within the supraoptic and paraventricular nuclei, results in impaired production and release of arginine vasopressin (AVP). Important regulating circuits of thirst sense and drive are regionally colocalized with AVP centers and therefore are also injured. Patients with central diabetes insipidus with impaired thirst response, defined as ADI, suffer from wide swings of plasma osmolality resulting in repeated hospitalization, numerous associated comorbidities, and significant mortality. Treatment recommendations are based largely on expert advice from case series owing to the rarity of disease prevalence. Acute disease management focuses on fixed dosing of antidiuretic hormone analogues and calculated prescriptions of obligate daily water intake. Long-term care requires patient/family education, frequent reassessment of clinical and biochemical parameters, as well as screening and treatment of comorbidities.

Pharmacological Dilutional Therapy Using the Vasopressin Antagonist Tolvaptan for Young Patients With Cystinuria: A Pilot Investigation

ObjectiveTo perform a pilot study of short-term safety, tolerability, and impact on urinary stone risk parameters of the vasopressin V2-receptor antagonist tolvaptan (which increases urinary excretion of free water) among adolescents and young adults with cystinuria. Materials and MethodsWe enrolled cystinuria patients age 12-25 years. Subjects were treated for 4 days at low-dose tolvaptan (0.3 mg/kg/day, maximum 30 mg) and 4 days at high dose (0.6 mg/kg/day, maximum 60 mg). Twenty-four-hour urine collections were done at baseline, day 3-4 of the dosing period, day 7-8 of the dosing period, and 3-6 days after washout. Primary outcome was cystine capacity (mg/L, target capacity > 0). Secondary outcomes included other urinary/serum parameters, tolerability, and thirst response. ResultsTwo females (17, 23 years) and 2 males (13, 24 years) were enrolled. Cystine capacity respectively went from baseline of −312, −82, −353, and −628 mg/L to 97, 111, 75, and −3 mg/L on high dose (Figure 1). Twenty-four-hour volume went from 1.96, 3.0, 2.1, and 0.91 L to 11.74, 6.5, 9.9, and 2.8 L on high dose (Figure 2). There were no abnormalities in serum electrolytes or liver enzymes. Subjects did experience extreme thirst (9/10 on visual scale), but none discontinued treatment or reduced dose. ConclusionDilutional therapy with tolvaptan increased both cystine capacity and urinary volumes. This treatment approach has the potential to reduce recurrence of stones in this population. Further investigation should study longer term effects and safety, and determine optimal dosing to improve tolerability.

Base de datos para Thirst response to post-exercise fluid replacement needs and controlled drinking

Capitán-Jiménez, C. &amp; Aragón-Vargas, L.F. (2016). Thirst Response to Post-Exercise Fluid Replacement Needs and Controlled Drinking. Pensar en Movimiento: Revista de Ciencias del Ejercicio y la Salud, 14(2), 1-16. Perceived thirst (TP) was evaluated as a dependent variable: can it distinguish among several levels of acute dehydration, is it reliable, and how does it respond to the ingestion of a fixed water volume post exercise? In a repeated-measures design, eight physically active students (24.5±3.6 years, mean±SD), reported to the laboratory on four non-consecutive days. They remained at rest or exercised at 32±3°C db and 65±6% rh to a randomly assigned dehydration equivalent to 1, 2, and 3% of body mass (BM). Following exercise, participants ingested a fixed water volume of 1.20% BM in 30 minutes; urine output, TP and plasma volume changes were assessed every 30 minutes over 3 hours. Post-exercise TP was not different before and after showering (p = 0.860), but it was significantly different among conditions (TP = 2.50 ± 0.45, 4.44 ± 0.72, 6.38 ± 0.82, and 8.63 ± 0.18 for 0, 1, 2, and 3% BM, p = 0.001). TP was associated with net fluid balance (rpart = -0.62, p &lt; 0.0001) but, soon after drinking, TP was the same regardless of dehydration (p &gt; 0.05). Thirst perception is valid and reliable in the absence of drinking but it responds inappropriately to water intake.

Exclusively drinking sucrose or saline early in life alters adult drinking behavior by laboratory rats

Proper fluid balance is critical for life. Learning plays an important role in shaping the appetitive behaviors required for drinking. Children often forego drinking plain water and instead consume beverages such as milk or juice. What effect this may have on adult thirst responses remains an open question. To model aspects of the human condition, we bred Sprague-Dawley rats and prevented the pups from obtaining fluid other than from nursing. Pups were weaned onto either tap water, 5% sucrose, or 0.45% saline, and given access to only that fluid for at least 7 weeks. We then measured intake of water or sucrose/saline in one-bottle tests after mild hypertonic saline (HS) injection, or overnight fluid deprivation, and in two-bottle tests after HS injection while rats were maintained on their respective fluids, and after all subjects had only water to drink for a week. We found that sucrose- and saline-maintained rats drank less water than did controls after the HS challenge. After overnight fluid deprivation, rats maintained on saline drank less water and more saline, but there was no difference in intake between water-maintained and sucrose-maintained rats. Differences in licking patterns, including more licks/burst for sucrose by sucrose-maintained rats were detected, even in cases when total intake was not different. These data provide evidence that adult rat water intake can be reduced by exclusively drinking sucrose or saline early in life.

Sports Dietitians Australia Position Statement: Nutrition for Exercise in Hot Environments.

It is the position of Sports Dietitians Australia (SDA) that exercise in hot and/or humid environments, or with significant clothing and/or equipment that prevents body heat loss (i.e.,exertional heat stress), provides significant challenges to an athlete's nutritional status, health, and performance. Exertional heat stress, especially when prolonged, can perturb thermoregulatory, cardiovascular, and gastrointestinal systems. Heat acclimation or acclimatization provides beneficial adaptations and should be undertaken where possible. Athletes should aim to begin exercise euhydrated. Furthermore, preexercise hyperhydration may be desirable in some scenarios and can be achieved through acute sodium or glycerol loading protocols. The assessment of fluid balance during exercise, together with gastrointestinal tolerance to fluid intake, and the appropriateness of thirst responses provide valuable information to inform fluid replacement strategies that should be integrated with event fuel requirements. Such strategies should also consider fluid availability and opportunities to drink, to prevent significant under- or overconsumption during exercise. Postexercise beverage choices can be influenced by the required timeframe for return to euhydration and co-ingestion of meals and snacks. Ingested beverage temperature can influence core temperature, with cold/icy beverages of potential use before and during exertional heat stress, while use of menthol can alter thermal sensation. Practical challenges in supporting athletes in teams and traveling for competition require careful planning. Finally, specific athletic population groups have unique nutritional needs in the context of exertional heat stress (i.e.,youth, endurance/ultra-endurance athletes, and para-sport athletes), and specific adjustments to nutrition strategies should be made for these population groups.

Osmotic Stimulation of Thirst in Men and Women (P15-017-19)

ObjectivesExamine potential sex differences in osmotically stimulated thirst. Methods60 healthy adults (30 female - measured in early follicular phase, age: 39 ± 8 y, weight: 78.2 ± 15.2 kg, body mass index: 26.9 ± 4.0 kg·m−2) were infused intravenously with 3% (HYPER) or 0.9% (ISO) NaCl for 120 min (0.1 ml·kg−1·min−1) in a counterbalanced, cross-over design. The same volume of saline was infused in both trials. Blood samples and thirst responses were collected prior to infusion and every 30 minutes. Plasma osmolality (POsm) and sodium (PNa) were measured. Thirst was assessed via a 180-mm visual analog scale consisting of a line with an anchor on the left side (0 mm, “not at all”) and a second anchor on the 125-mm mark with the label “extremely”. ResultsFrom 0 min to 120 min in the HYPER trial, PNa increased from 136 ± 2 mmol ·L−1 to 146.5 ± 3 mmol ·l−1 (P < 0.001). Similarly, POsm and thirst increased significantly from 286 ± 3 mmol·kg−1 to 305 ± 4 mmol·kg−1 (P < 0.001) and from 38 ± 29 mm to 88 ± 35 mm (P < 0.001), respectively. During the ISO trial, PNa (0 min: 135.9 ± 1.9; 120 min: 137.6 ± 1.6 mmol·L−1), POsm (0 min: 285 ± 4 mmol·kg−1; 120 min: 287 ± 3 mmol·kg−1), and thirst (0 min: 30 ± 27 mm; 120 min: 44 ± 32 mm) remained unchanged (P > 0.05). POsm at the end of the infusion did not differ between men and women for the HYPER (men: 306 ± 5 mmol·kg−1; women: 305 ± 3 mmol·kg−1) or ISO (men: 288 ± 3 mmol·kg−1; women: 288 ± 3 mmol·kg−1) trials. When thirst responses were split by sex women exhibited greater thirst (98 ± 27 mm) than men (77 ± 38 mm) at the end of the HYPER trial (P < 0.0001), but not at the end of the ISO trial (women: 43 ± 32 mm, men 44 ± 31 mm; P > 0.05). ConclusionsThese data suggest that similar hypertonic stimulus may lead to greater thirst stimulation in women. Funding SourcesThis study was funded by Danone Research.

Castaway cottonmouths depend on rain to slake thirst

Castaways usually meet their fate by washing ashore on a desert island, but not the cottonmouth pit vipers (Agkistrodon conanti) of the Cedar Keys, Florida. ‘Our understanding is that these islands formed in the recent past as relic sand dunes that were connected to the mainland via dry land until sea levels rose’, says Mark Sandfoss from the University of Florida, USA. And when the reptiles found themselves cut off from sources of fresh water, they really were left high and dry. ‘Cottonmouths are almost exclusively found in freshwater habitats’, explains Sandfoss; which made him and his thesis advisor, Harvey Lillywhite, wonder how the marooned serpents manage their thirst when surrounded by undrinkable seawater.‘Harvey has been collecting drinking data on free-ranging cottonmouths for decades’, says Sandfoss, describing how Lillywhite picks up the vipers with a hook, weighs them and offers them a bowl of water to drink. He then reweighs the animals immediately after they have slaked their thirst to determine how much water they have consumed. After joining Lillywhite's lab in 2013, Sandfoss began comparing Lillywhite's observations of how likely the snakes were to drink with the amount of rainfall on the islands and found that the animals that had experienced the longest drought gulped down the largest volume, while snakes that had experienced rainfall in recent days were less eager to drink. However, when the scientists compared the island cottonmouths’ drinking habits with those of their mainland cousins, which live in swamps and rivers, 64% of the island animals were dehydrated while only 24% of their mainland cousins needed a drink. The duo realised that the island cottonmouths depend on rainwater and go thirsty between rainfalls.The scientists then wondered whether the water-deprived castaways were able to suppress their thirst more than the mainland population, so Sandfoss allowed island and mainland snakes to go thirsty and then recorded the animals’ mass when they decided that they needed a drink. ‘We found a large variation in the thirst responses of snakes from the two populations, with some snakes drinking after losing less than 2% mass while others from the same population did not drink until they had lost more than 12%’, says Sandfoss. However, when the scientists compared the two groups of animals, there was no difference in their thirst threshold, so the castaways don't seem to have altered their thirst tolerance in response to their tropical-island lifestyle.The pair then investigated how the two populations would react when offered a drink of salt water. ‘We know that even the most well-adapted sea snakes require fresh water for drinking and this made us think that insular cottonmouths would not be able to rely on seawater’, says Sandfoss. Discovering quickly that both populations turned up their noses at full-strength – and even 25% – seawater, Sandfoss then offered thirsty mainland and island cottonmouths increasingly dilute saltwater drinks and found that most of the island snakes (19) refused the salty drinks: only 7 chanced a sip. However, the mainland cottonmouths were far less discriminating, with 6 sipping the saltiest (30%) water and only 7 holding off until they were offered fresh water. Also, when the duo compared the water preferences of newborns, it seemed that the island youngsters had inherited their parents’ aversion to salt water.Castaway cottonmouths have evolved the ability to detect and avoid drinking seawater, even though the prospect may seem tempting when the rains fail, but do not supress their thirst, and Sandfoss is keen to find out how the marooned snakes sniff out the difference between fresh and salt water when feeling parched.

Recurrent Polyuria

Recurrent Polyuria

Abstract 107: Neurons in the Organum Vasculosum of the Lamina Terminalis Sense NaCl and Angiotensin II to Regulate Sympathetic Nerve Activity and Arterial Blood Pressure

The organum vasculosum of the lamina terminalis (OVLT) contains specialized neurons that sense changes in extracellular NaCl concentrations to regulate sympathetic nerve activity (SNA) and arterial blood pressure (ABP). However, OVLT neurons also abundantly express angiotensin II (AngII)-type I receptors. Therefore, we performed a series of in vitro and in vivo studies in adult male Sprague-Dawley rats to determine whether OVLT neurons sense both NaCl and AngII to impact SNA and ABP. First, in vitro whole-cell recordings revealed the majority of OVLT neurons (66%, 23/35) showed an increased discharge frequency to both +7.5mM NaCl (1.1±0.2 to 2.2±0.3Hz, P&lt;0.001) and 100pM AngII (1.3±0.3 to 2.2±0.3Hz, P&lt;0.001). Second, in vivo single-unit recordings demonstrate the majority of OVLT neurons (61%, 11/18) displayed an increase in cell discharge to intracarotid injection of 0.5M NaCl (3.6±0.6 to 9.0±1.6Hz, P&lt;0.01) and 200ng AngII (3.2±0.7 to 9.2±1.9Hz, P&lt;0.01). Third, optogenetic inhibition of OVLT neurons (rAAV2-CaMKII-eNpHR3.0-mCherry, 5x10 12 particles/mL, 561nm, 10mW) attenuated thirst responses to IV infusion of 2M NaCl (1.25mL/30min; Laser OFF: 6.1±0.5mL vs ON: 2.0±0.7mL, P&lt;0.05) and AngII (Laser OFF 7.2±0.7mL vs ON: 2.2±1.2mL; n=5 per group, P&lt;0.05). Fourth, OVLT injection (20nL) of 0.5M NaCl or 10pmol AngII increased SNA (121±6% or 117±5%, n=4/group; P&lt;0.05 respectively) and mean ABP (7±1 or 9±2mmHg, n=4/group; P&lt;0.05 respectively). To determine whether chronic activation of OVLT neurons produces hypertension, rats received an OVLT injection of rAAV2-hSyn-HM3D(Gq)-mCherry (3x10 12 particles/mL, 50nL) and given access to 0.1% NaCl chow and 0.9% NaCl drinking solution. After 4 weeks, daily administration of clozapine-N-oxide to the drinking solution (3mg/kg/day) significantly increased 24-h fluid intake (baseline: 60±10mL vs Day 7: 178±29mL; n=6, P&lt;0.01) and 24-h mean ABP (baseline: 97±2mmHg vs Day 7: 108±1 mmHg; n=6, P&lt;0.05). Ganglionic blockade with hexamethonium (30mg/kg, ip) produced a greater fall in mean ABP at Day 7 (baseline: -38±6 mmHg vs Day 7: -53±5 mmHg, P&lt;0.05). These findings suggest OVLT neurons sense both NaCl and AngII to regulate body fluid homeostasis and SNA to produce a sympathetically-mediated hypertension.

INFLUENCE OF LOW-SODIUM DIET MANAGEMENT ON THIRST RESPONSE IN END STAGE RENAL DISEASE PATIENTS WITH HEMODIALYSIS

Background: Patients with hemodialysis often have difficulty in controlling their fluid intake although the obedience to follow fluid and dietary restriction is the key of hemodialysis success management.&#x0D; Objective: The aim of this study was to examine the effect of low-sodium diet management on thirst response in end stage renal disease patients with hemodialysis.&#x0D; Methods: This was a quasi-experimental study with pre-posttest with control group design. Using consecutive sampling 88 respondents were selected, which 44 assigned in each group. Thirst distress scale and visual analog scale questionnaire were used for data collection. Wilcoxon and Mann Whitney test were used for statistical analysis.&#x0D; Results: Of the total of respondents, thirty-seven respondents experienced a decrease in thirst distress scale with p= 0.000 (p &lt;0.05); and 30 respondents experienced a decrease in visual analog scale with p=0.000 after given low sodium diet management. There was difference of thirst distress scale score (p=0.008) and visual analog scale of thirst score (p=0.048) between intervention and control group. The importance of continuous of diet education with counseling and home visit can increase self-management behaviors.&#x0D; Conclusion. Low sodium diet management could reduce the thirst response in end stage renal disease patients with hemodialysis.