Increase In Plasma Sodium Concentration Research Articles

Prevalence of Admission Hyponatremia in Patients With Diabetes Treated With and Without an SGLT2 inhibitor.

Hyponatremia often reflects a free water excess. Sodium/glucose cotransporter 2 (SGLT2) inhibitors increase free water excretion through glucose-induced osmotic diuresis. In 2 randomized double-blind, placebo-controlled trials in patients with the syndrome of inappropriate antidiuresis (SIAD), we showed that empagliflozin increased plasma sodium concentration more effectively than placebo. We hypothesized that long-term therapy with SGLT2 inhibitors might reduce the prevalence of hyponatremia on hospital admission. In this retrospective analysis, we extracted data from adult patients with type 2 diabetes (T2DM) hospitalized at the University Hospital Basel between 2015 and 2020. Patients with an SGLT2 inhibitor on admission were matched 1:1 according to age, gender, diagnosis of heart failure, and principal diagnosis to patients without an SGLT2 inhibitor on admission. The primary outcome was the prevalence of hyponatremia (plasma sodium concentration corrected for glycemia <135 mmol/L) on admission. We analyzed 821 patients with T2DM treated with and 821 patients with T2DM without an SGLT2 inhibitor on admission. Hyponatremia prevalence on admission was 9.9% in the treated group, and 8.9% in the matched control group (P = .554), in other words, the risk for hyponatremia did not differ (multivariable adjusted odds ratio 1.08, 95% CI 0.72-1.44, P = .666). There was no difference in the median (interquartile range) plasma sodium concentration between the groups (treated 140 mmol/L [138-142], controls 140 mmol/L [138-142]; P = .1017). Based on these retrospective findings, treatment with SGLT2 inhibitors does not prevent hyponatremia. However, prospective randomized data suggest their efficacy at a higher dosage in overt SIAD.

Continuous hemodialysis with citrate anticoagulation and standard dialysate for managing acute kidney injury in patients with moderate to severe hyponatremia-A retrospective study.

The safety of continuous veno-venous hemodialysis (CVVHD) with citrate-calcium anticoagulation for acute kidney injury (AKI) with coincident hyponatremia remains unclear. We aimed to explore the feasibility of CVVHD with standard dialysate and citrate-calcium anticoagulation in hyponatremic critically ill AKI patients. Thirty-seven of the 493 critically ill AKI patients requiring CVVHD and admitted to our intensive care unit during a 10-year period had hyponatremia (<130mmol/L) and were included in this retrospective study. All patients received CVVHD with citrate-calcium anticoagulation and standard commercial dialysate and plasma sodium concentrations were frequently controlled until death or CVVHD discontinuation. Clinical data, mortalities and cases of central pontine myelinolysis within one-year follow-up were recorded. Median plasma sodium concentration was 127 (IQR 124-129)mmol/L at CVVHD initiation. CVVHD duration was median 3 (IQR 1.5-5.5)days and the mean daily sodium load of the trisodium citrate solution during the first 3days of CVVHD was 1754 (SD 730)mmol. The plasma sodium concentration increased a median 8 (IQR 5-10)mmol/L during the first 24hours of CVVHD and excessively high plasma sodium correction (>8mmol/L/24h) was observed in 18 (48.6%) patients. However, increased mortality in association to rapid plasma sodium correction was not observed in this study. CVVHD using standard citrate-calcium anticoagulation effectively increased plasma sodium concentration in this study. However, excessively high plasma sodium correction was observed in half of the patients and the sodium load provided by the standard citrate anticoagulation solutions was substantial.

Severe Hyponatremia and Continuous Renal Replacement Therapy: Safety and Effectiveness of Low-Sodium Dialysate

Rationale & ObjectiveIn patients with severe hyponatremia in the setting of acute kidney injury or end-stage kidney disease, continuous renal replacement therapy (CRRT) using standard-sodium (140 mEq/L) fluids may lead to excessively rapid correction of plasma sodium concentration. Use of dialysate and replacement fluids with reduced sodium concentrations can provide a controlled rate of correction of plasma sodium concentration.Study DesignWe performed a single-center retrospective analysis of the safety and effectiveness of this approach in patients with plasma sodium concentrations ≤ 126 mEq/L who underwent CRRT for 24 or more hours using low-sodium (119 or 126 mEq/L) dialysate and replacement fluids. Change in plasma sodium level was assessed at 24 and 48 hours after initiation of low-sodium CRRT and at the end of treatment.Setting & ParticipantsBetween January 2016 and June 2018, a total of 23 hyponatremic patients underwent continuous venovenous hemodiafiltration using low-sodium dialysate and replacement fluids; 4 patients were excluded from analysis because of CRRT duration less than <24 hours.ResultsThe 19 patients included in the study had a mean age of 56 years, 11 (58%) were men, and 15 (79%) were white. The initial mean plasma sodium level was 121 mEq/L and the initial CRRT effluent dose was 27 mL/kg/h. Only 2 (11%) patients had an increase in plasma sodium concentration > 6 mEq/L at 24 hours. Mean changes in plasma sodium levels at 24 and 48 hours and at the time of CRRT discontinuation were 3, 3, and 6 mEq/L, respectively. None of the patients developed osmotic demyelination syndrome.LimitationsKey limitations were small sample size and lack of a control group.ConclusionsUse of low-sodium dialysate and replacement fluids is a safe strategy for the prevention of overly rapid correction of plasma sodium levels in hyponatremic patients undergoing CRRT.

Food Products That May Cause an Increase in Blood Pressure.

To review latest reports of the food products which might increase blood pressure and therefore might participate in the pathogenesis of hypertension. Results of clinical study suggest that consumption of high-sodium food leads to transient increase in plasma sodium concentration. This is accompanied by blood pressure increase. Results of both clinical and experimental studies suggest direct vasculotoxic effects of sodium. Increased plasma sodium concentration could mediate its effects on blood pressure by changes in endothelial cell stiffness and glycocalyx integrity. Energy drinks are non-alcoholic beverages with increasing popularity. Clinical, interventional, randomized, placebo controlled, and cross-sectional studies showed that energy drinks may increase arterial blood pressure. Blood pressure increase after exposure for the energy drinks is mainly related to the caffeine content in these drinks. Many case reports were published concerning the clinically significant increase in blood pressure caused by the consumption of liquorice root or food products containing liquorice, such as candies, tea, Pontefract cookies, and chewing gum. Liquorice contains a precursor of glycyrrhetic acid. Glycyrrhetic acid reduces the activity of the 11β-hydroxysteroid dehydrogenase type 2 (11ß-HSD2) isoenzyme, which leads to activation of the mineralocorticoid receptor by cortisol in the distal convoluted tubule resulting in hypertension, hypokalemia, and metabolic alkalosis. The relationship between chronic alcohol intake and blood pressure is well established on the basis of a diverse body of evidence including animal experiments, epidemiological studies, mendelian randomization studies, and interventional studies. Results of recent studies suggested that binge drinking (i.e., episodic consumption of a very high amount of alcohol beverages) has pronounced hypertensinogenic effects. Recently, it was documented that also low doses of alcohol may increase the risk of cardiovascular complications. Therefore, the amount of alcohol consumption that is safe is zero. High-salt food products, energy drinks, food products containing liquorice, and alcoholic beverages have hypertensinogenic properties. Patients with hypertension and other cardiovascular diseases should avoid even accidental consumption of these food products.

Calcium sensing receptor exerts a negative regulatory action toward vasopressin-induced aquaporin-2 expression and trafficking in renal collecting duct.

Vasopressin (AVP) plays a major role in the regulation of water homeostasis by its antidiuretic action on the kidney, mediated by V2 receptors. An increase in plasma sodium concentration stimulates AVP release, which in turn promotes water reabsorption. Upon binding to the V2 receptors in the renal collecting duct, AVP induces the expression and apical membrane insertion of the aquaporin-2 (AQP2) water channels and subsequent water reabsorption. AVP regulates two independent mechanisms: the short-term regulation of AQP2 trafficking and long-term regulation of the total abundance of the AQP2 protein in the cells. On the other hand, several hormones, acting through specific receptors, have been reported to antagonize AVP-mediated water transport in kidney. In this respect, we previously described that high luminal Ca2+ in the renal collecting duct attenuates short-term AVP-induced AQP2 trafficking through activation of the Ca2+-sensing receptor (CaSR). This effect is due to reduction of AVP-dependent cAMP generation and possibly hydrolysis. Moreover, CaSR signaling reduces AQP2 abundance both via AQP2-targeting miRNA-137 and the proteasomal degradation pathway. This chapter summarizes recent data elucidating the molecular mechanisms underlying the physiological role of the CaSR-dependent regulation of AQP2 expression and trafficking.

Pannexin 1 channels in renin expressing cells regulate RAAS and blood pressure

The homeostatic regulation of blood pressure by renin lineage cells in the renal vasculature and the adrenal zona glomerulosa (ZG), is crucial for controlling tissue renin expression and adrenocortical aldosterone synthesis. In the renal vasculature, renin lineage cells respond to changes in blood pressure by differentiating and re‐expressing their fetal renin gene program to compensate for lowered blood pressure. In the adrenal cortex, ZG cells of the renin lineage centripetally turnover, differentiating from an aldosterone synthetic program to a glucocorticoid synthetic one, thus maintaining steady state aldosterone production. The cellular signals coordinating these transitions is unclear, but evidence from our lab posits a role for purinergic signaling mediated by Pannexin 1 channels. We hypothesized that Pannexin 1 (Panx1) channels regulate purinergic communication and cell differentiation in the renal vasculature and adrenal cortex to regulate RAAS and blood pressure homeostasis. To test this hypothesis, we generated a novel renin cell Panx1 knockout mouse (Ren1‐Px1 KO). At baseline, mice exhibit no differences in kidney size, morphology, or plasma renin concentration. However, Ren1‐Px1 KO mice have increased plasma sodium concentration, reduced urine volume, and a significant elevation in aldosterone levels, which corresponded with aberrant expression of aldosterone synthetic enzyme (CYP11B2) and ZG cell differentiation in the adrenal cortex. Using radiotelemetry, we measured blood pressure in Ren1‐Px1 KO mice, which were hypertensive at baseline. Lastly, we assessed renin dynamics in the kidney when blood pressure is lowered. Ren1‐Px1 KO mice retain the capacity to secrete renin at baseline, but fail to completely recruit tissue renin expression in the renal vasculature. We conclude that loss of Panx1 from renin lineage cells causes activation of RAAS primarily by influencing ZG trans‐differentiation, despite changes in renal renin dynamics. Thus, Panx1 channels may be a novel regulator of long term blood pressure control.Support or Funding Information1 F31 HL1376270/NHLBI NIH P01 HL120840/NHLBI NIHThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Syndrome of Inappropriate Antidiuretic Hormone Secretion in a Mini-Breed Puppy Associated With Aspiration Pneumonia

A 3-month-old intact male Prague ratter was presented to the emergency service for evaluation of progressive lethargy, weakness, coughing and labour breathing after an episode of resistance to oral deworming. The patient exhibited depression, increased respiratory effort and cyanosis at initial presentation. Results of first diagnostic work-up (complete blood cell count, biochemistry panel and thoracic x-rays) were all consistent with aspiration pneumonia. The puppy was initially treated with balanced isotonic crystalloids, broad spectrum antibiotics, nebulization with thoracic coupage and was transferred to an infant incubator with a sustained FiO2 of 40-50%. Twenty-four hours after ICU admission the patient's condition suffered a worsening and the dog was orthopneic, severely depressed with episodes of intermittent dysphoria and seizuring. New thoracic radiographs and several samples of blood and urine were collected to go further in the diagnostic workup revealing severe hyponatremia, severe plasma hypotonicity, high natriuresis and metabolic acidosis with a worsening of the radiological pulmonary pattern. Based on these new clinical findings a diagnosis of SIADH was established. Emergency treatment with hypertonic 3% saline solution and loop diuretics was started like a sodium supplement and to inhibit water resorption in renal tubules, thus reducing the volume overload. The goal of this treatment was to achieve a progressive and controlled increase of plasma sodium concentration and promoting the excretion of positive body water imbalance. The patient's condition improved clinically over the following days, treatment was progressively discontinued and the dog was discharged 7 days after admission. To the author's knowledge this is the first report of a puppy younger than 12 weeks with respiratory distress developing SIADH associated to aspiration pneumonia.

Dynamic Response to Long‐Term Sodium Loading and Restriction

Plasma sodium concentration is controlled within very narrow limits. During changes in sodium intake, plasma sodium concentration deviates minimally from its normal value. Sodium intake was increased from a normal to a high level (208 % of normal) for 5 days and then dropped to a low level (13% of normal) for subsequent 5 days in He et al's experimental study (Hypertension.38:321‐325, 2001). Plasma renin, aldosterone and sodium concentrations were measured. He et al. reported decreases in renin and aldosterone concentrations and a small increase in plasma sodium concentration during sodium loading. During the subsequent 5 days of sodium intake decrease, there was an increase in plasma renin and aldosterone concentrations and a small decrease in plasma sodium concentration. The mathematical model we developed was tested with He et al.'s experimental findings in our previous study. And it was shown that the model gave similar results to the experimental work. In this study, to analyze the response dynamics in detail, the rate of change (derivative) of plasma renin, aldosterone and sodium concentrations during sodium loading and restriction were calculated by using the same model. According to the model, the maximum value of the rate of change of plasma renin, aldosterone and sodium concentrations during sodium restriction is larger than during the sodium loading condition. The possible reason of this simulation result is that the absolute change in the sodium intake from a high level to a low level is larger than the change in the sodium intake from a normal to a high level during sodium loading in the model.

Chronic Central Infusion of Hypertonic NaCl Increase Blood Pressure Variability and Exaggerates Sympathetic Reflexes

Recent studies indicate that dietary salt loading increases blood pressure variability (BPV) and exaggerates sympathetic reflexes in salt‐resistant animals. This effect was attributed to a central action of sodium as high salt diet increased plasma sodium concentration and lesion of the forebrain hypothalamus prevented these responses. Since dietary salt loading also affects neurohumoral systems, the present study tested whether central hypernatremia can increase BPV and exaggerate sympathetic reflexes. Sprague‐Dawley rats were implanted with telemetry units and infused with artificial cerebrospinal fluid (aCSF, n=6) or 1M NaCl (n=6, 6uL/h) for 10 days. Baseline blood pressure (BP) did not differ animals infused with 1M NaCl vs aCSF (99±3 vs 99±1 mmHg). Although mean BP did not change after 10 day infusion of 1M NaCl vs aCSF (3±1 vs ‐3±1 mmHg), the SD of 24‐h systolic BP was significantly greater in animals infused with 1M NaCl versus aCSF (9.8±1.2 vs 6.4±1.0, P&lt;0.05). Under Inactin anesthesia, stimulation of sciatic afferents (1ms, 500µA, 1‐20Hz) produced frequency‐dependent increases in renal SNA, splanchnic SNA, and mean BP in both groups. However, animals infused with 1M NaCl vs aCSF displayed significantly larger increases in renal SNA (5Hz: 91±17% vs 43±15%, P&lt;0.05), splanchnic SNA (5Hz: 111±25% vs 31±3%, P&lt;0.05), and mean BP (5Hz: 25±3 vs 15±3mmHg, P&lt;0.05). Plasma renin activity at rest was not different between groups (1M: 3.1±1.0 vs aCSF: 3.7±1.2 ng AngI/mL/min). Collectively, these findings suggest that central hypernatremia increases BPV and exaggerates sympathetic reflexes in salt‐resistant, normotensive rats.

Acute hypernatremia promotes anxiolysis and attenuates stress-induced activation of the hypothalamic–pituitary–adrenal axis in male mice

Previous investigation by our laboratory found that acute hypernatremia potentiates an oxytocinergic tone that inhibits parvocellular neurosecretory neurons in the paraventricular nucleus of the hypothalamus (PVN), attenuates restraint-induced surges in corticosterone (CORT), and reduces anxiety-like behavior in male rats. To investigate the neural mechanisms mediating these effects and extend our findings to a more versatile species, we repeated our studies using laboratory mice. In response to 2.0M NaCl injections, mice had increased plasma sodium concentrations which were associated with a blunted rise in CORT subsequent to restraint challenge relative to 0.15M NaCl injected controls. Immunofluorescent identification of the immediate early gene product Fos found that 2.0M NaCl treatment increased the number of activated neurons producing oxytocin in the PVN. To evaluate the effect of acute hypernatremia on PVN neurons producing corticotropin-releasing hormone (CRH), we used the Cre-lox system to generate mice that produced the red fluorescent protein, tdTomato, in cells that had Cre-recombinase activity driven by CRH gene expression. Analysis of brain tissue from these CRH-reporter mice revealed that 2.0M NaCl treatment caused a dramatic reduction in Fos-positive nuclei specifically in CRH-producing PVN neurons. This altered pattern of activity was predictive of alleviated anxiety-like behavior as mice administered 2.0M NaCl spent more time exploring the open arms of an elevated-plus maze than 0.15M NaCl treated controls. Taken together, these results further implicate an oxytocin-dependent inhibition of CRH neurons in the PVN and demonstrate the impact that slight elevations in plasma sodium have on hypothalamic–pituitary–adrenocortical axis output and anxiety-like behavior.

Inhibition of natriuresis in median eminence polydipsia: effects after intake of diets with different osmolalities and after hypertonic NaCl administration.

Lesions in the hypothalamic median eminence (ME) induce polydipsia and polyuria in male rats. A first experiment was designed to examine the effect of salt consumption (standard 0.25 percent Na+ vs. low-salt 0.04 percent Na+ diet) on the fluid-electrolytic balance (plasma sodium, urinary sodium excretion, urine osmolality) and water intake of ME polydipsic animals. In the first 6 h post-surgery, the natriuretic response was higher in ME-lesioned animals than in control groups. At 24 h post-surgery, however, less sodium was excreted by ME rats fed with a standard salt diet (ME/SS), despite showing no decrease in salt intake, and they evidenced an increase in plasma sodium concentration and water intake. Urine osmolality was significantly higher in control animals than in either ME-lesioned group. In experiment 2, hypertonic NaCl administration (2 ml/2M) increased the polydipsic behavior of ME-lesioned but not control rats (day 2). Animals deprived of food/salt showed a significant reduction (on day 2) in the initial (day 1) polydipsia, which increased on day 3 when the animals had access to a standard-salt diet. These results suggest that the reduced natriuretic response and the consequent sodium retention observed in ME animals may exacerbate the hydromineral imbalance of this polydipsic syndrome.

Effect of orally administered sodium bicarbonate on caecal pH

Caecal acidosis is a central event in the metabolic cascade that occurs following grain overload. Buffering the caecal acidosis by enterally administered sodium bicarbonate (NaHCO3 ) may be beneficial to affected horses. To determine the effect and duration of enterally administered NaHCO3 on caecal pH in healthy horses. Experimental study using horses with caecal cannulas. Nine horses had been previously fitted with a caecal cannula. Six horses received 1.0 g/kg bwt NaHCO3 and 3 control horses were given 3 l of water via nasogastric tube. Clinical parameters, water consumption, venous blood gases, caecal pH, faecal pH and faecal water content were measured at 6 h intervals over a 36 h study period. Horses that received enterally administered NaHCO3 had significantly increased caecal pH that lasted the duration of the study. Treated horses increased their water intake, and developed metabolic alkalaemia, significantly increased plasma sodium concentrations and significantly decreased plasma potassium concentrations. Enterally administered NaHCO3 may be beneficial in buffering caecal acidosis.

Acute Hypernatremia Exerts an Inhibitory Oxytocinergic Tone That Is Associated With Anxiolytic Mood in Male Rats

Anxiety disorders are the most common psychiatric illnesses and are associated with heightened stress responsiveness. The neuropeptide oxytocin (OT) has garnered significant attention for its potential as a treatment for anxiety disorders; however, the mechanism mediating its effects on stress responses and anxiety is not well understood. Here we used acute hypernatremia, a stimulus that elevates brain levels of OT, to discern the central oxytocinergic pathways mediating stress responsiveness and anxiety-like behavior. Rats were rendered hypernatremic by acute administration of 2.0 M NaCl and had increased plasma sodium concentration, plasma osmolality, and Fos induction in OT-containing neurons relative to 0.15 M NaCl-treated controls. Acute hypernatremia decreased restraint-induced elevations in corticosterone and created an inhibitory oxytocinergic tone on parvocellular neurosecretory neurons within the paraventricular nucleus of the hypothalamus. In contrast, evaluation of Fos immunohistochemistry determined that acute hypernatremia followed by restraint increased neuronal activation in brain regions receiving OT afferents that are also implicated in the expression of anxiety-like behavior. To determine whether these effects were predictive of altered anxiety-like behavior, rats were subjected to acute hypernatremia and then tested in the elevated plus maze. Relative to controls given 0.15 M NaCl, rats given 2.0 M NaCl spent more time in the open arms of the elevated plus maze, suggesting that acute hypernatremia is anxiolytic. Collectively the results suggest that acute elevations in plasma sodium concentration increase central levels of OT, which decreases anxiety by altering neuronal activity in hypothalamic and limbic nuclei.

Diagnosis and treatment of adipsic diabetes insipidus accompanied with intracranial calcification

To summarize our experience in the management of adipsic central diabetes insipidus(ADI) accompanied with intracranial calcification. The clinical data of one ADI patient accompanied with intracranial calcification who was treated in our hospital since December 2011 were retrospectively summarized. The 24-hour urine volume was 800 ml. She didn't feel thirsty even with increased plasma sodium concentration(153 mmol/L) and blood osmotic pressure(333 mmol/L) . Combined water deprivation and vasopressin test revealed the diagnosis of central diabetes insipidus. The high intensity signal(on T1-weighted magnetic resonance imaging) in the posterior lobe of pituitary gland was found. Computed tomography showed calcifications in the bilateral basal ganglia.Serum cytomegalovirus IgG was positive. She was treated with desmopressin and asked for regular water intake regardless of the adipsia. The plasma sodium concentration was still below 150 mmol/L during the 4-month follow-up. Routine adipsia evaluation and combined water deprivation and vasopressin test are critical for the diagnosis and treatment of ADI. Past insidious intracranial cytomegalovirus infection may explain the cause of ADI and calcification.

Acute hypernatremia increases the discharge of sympathetic‐vasomotor neurons in the rostral ventrolateral medulla

Sympathetic‐regulatory neurons of the rostral ventrolateral medulla (RVLM) play a pivotal role in salt‐sensitive hypertension. Previous studies have demonstrated that several models of salt‐sensitive hypertension are associated with increases in plasma or cerebrospinal fluid sodium concentration. The purpose of the present study was to determine whether acute increases in plasma sodium concentration activate sympathetic‐vasomotor RVLM neurons. Extracellular single‐unit recordings were performed in urethane‐anesthetized, male Sprague‐Dawley rats (290–350 g). Intracarotid injection of hypertonic saline (250 mM NaCl, 100 uL over 10 s) significantly increased RVLM discharge in 83% (5/6) of neurons (4.1±1.4 to 9.6±2.9 Hz, P&lt;0.01), elevatd renal SNA (38±10%, P&lt;0.01), and increased arterial blood pressure (14±2 mmHg, P&lt;0.01). These neurons were barosensitive as inflation of an aortic cuff increased arterial blood pressure (31±2 mmHg) but decreased RVLM neuronal discharge (4.2±1.4 to 1.5±0.5 Hz, P&lt;0.01). All neurons were antidromically activated from the spinal cord and had an average conduction velocity of 3.5±0.8 m/s. Intracarotid injection of isotonic saline had no effect on any variable. These findings suggest that acute increases in plasma sodium concentration activate sympathetic‐regulatory neurons in the RVLM.

Hypothalamic cocaine- and amphetamine-regulated transcript and corticotrophin releasing factor neurons are stimulated by extracellular volume and osmotic changes

Several studies suggest that hypothalamic cocaine- and amphetamine-regulated transcript (CART) may interact with the hypothalamic-pituitary-adrenal (HPA) axis in the control of neuroendocrine function and may also participate in cardiovascular regulation. Therefore, this study aimed to evaluate, in experimental models of isotonic (I-EVE) and hypertonic (H-EVE) extracellular volume expansion and water deprivation (WD), the activation of CART- and corticotrophin releasing factor (CRF)-immunoreactive neurons, as well as the relative expression of CART and CRF mRNAs in the paraventricular (PVN) and supraoptic (SON) nuclei of the hypothalamus. Both H-EVE (0.30M NaCl, 2mL/100g of body weight, in 1 minute) and 24 hours of WD significantly increased plasma sodium concentrations, producing, respectively, either an increase or a decrease in extracellular volume. I-EVE (0.15M NaCl, 2mL/100g of body weight, in 1 minute) evoked a significant increase in the circulating volume accompanied by unaltered plasma concentrations of sodium. CART-expressing neurons of both magnocellular and parvocellular hypothalamic divisions were activated to produce Fos in response to H-EVE but not in response to I-EVE. Furthermore, increased expression of CART mRNA was found in the PVN of H-EVE but not I-EVE rats. These data show for the first time that EVE not only activates hypothalamic CRF neurons but also increases CRF mRNA expression in the PVN. In contrast, WD increases the number of CART-immunoreactive neurons activated to produce Fos in the PVN and SON but does not change the number of neurons double labeled for Fos and CRF or expression of CRF mRNA in the PVN. These findings provided new insights into the participation of CART in diverse processes within the PVN and SON, including its possible involvement in activation of the HPA axis and cardiovascular regulation in response to changes in extracellular volume and osmolality.

Expression of the renin angiotensin system genes in the kidney and heart of ISIAH hypertensive rats

The content of mRNA of renin-angiotensin system (RAS) genes was measured in the kidney and heart of hypertensive ISIAH and normotensive WAG rats using the real-time PCR. A statistically significant decrease in the mRNA level of RAS genes was registered in the kidney of ISIAH rats, including Ren (by 45%), Ace (43%), AT1A (34%), COX-2 (50%). The level of myocardial expression of AT1A decreased by 28% while Ace expression increased by 80%. These results suggest reduction of renal RAS basal activity in the hypertensive ISIAH rats, and therefore this strain of rats may be referred to the group of models of low-renin hypertension. The ISIAH rats were also characterized by a two-fold increase in the connective tissue sodium concentration and also by a small (but statistically significant) increase in plasma sodium concentration (139 ± 0.3 mmol/l versus 136 ± 0.25 mmol/l in WAG rats). These results together with a tendency to a decrease of plasma aldosterone level also support existence of a classical low-renin hypertension in the ISIAH rats. It is suggested that altered function of renal ion channels represents a basis for the development of low renin hypertension in the ISIAH rats. In addition, impairments in renal system of NO synthesis may also contribute to the pathogenesis of arterial hypertension in the ISIAH rats.

Maternal renal dysfunction in sheep is associated with salt insensitivity in female offspring

To examine the programming effects of maternal renal dysfunction (created by subtotal nephrectomy in ewes prior to mating; STNx), renal and cardiovascular function were studied in 6-month-old male and female offspring of STNx and control pregnancies. After studies were conducted on a low salt diet (LSD) some female offspring underwent salt loading (0.17 M NaCl in the drinking water for 5-7 days; HSD). On LSD both male and female offspring of STNx had similar mean arterial pressures (MAP), heart rates, cardiac outputs and renal function to those measured in offspring of control ewes. In female STNx offspring on a HSD, plasma sodium levels increased and haematocrits fell, indicating volume expansion (P < 0.05). Plasma renin levels were not suppressed despite the increases in plasma sodium concentrations, but aldosterone levels were reduced. In control animals plasma renin levels fell (P < 0.05) but there was no change in plasma aldosterone concentrations. There was a positive relationship between GFR and MAP which was present only in female STNx offspring. In conclusion, in STNx offspring there was an impaired ability to regulate glomerular filtration independent of arterial pressure, renin release was insensitive to a high salt intake and control of aldosterone secretion was abnormal. This study provides evidence of abnormal programming of the renin-angiotensin system and glomerular function in offspring of pregnancies in which there is impaired maternal renal function.

Acute Effects of Sodium Ingestion on Thirst and Cardiovascular Function

Sweating during exercise, especially during exercise in the heat, leads to sodium and water losses, and the quantity of these losses depends upon the intensity and duration of the activity, genetic predisposition and conditioning of the individual, and environmental factors. In athletes, adequate sodium intake is necessary to maintain fluid balance during training and competition. To ensure the precise regulation of volume and osmolality of body fluids, a number of integrated neural and hormonal systems have evolved to control thirst and sodium appetite. These systems respond to stimuli that arise from a deficit of fluid arising in both the intracellular and extracellular fluid compartments or to systemic hypertonicity. Thirst is highly sensitive to increases in plasma sodium concentration and osmolality, requiring only a 2%-3% increase to induce feelings of thirst. A larger change in plasma volume (10%) is required to induce thirst if there is no concomitant change in plasma sodium concentration. If plain water is used to replenish body water, plasma volume is preferentially restored over the interstitial and intracellular fluid space, suppressing plasma sodium concentration and removing the dipsogenic drive long before total body fluid has been restored. During or after dehydrating exercise, sodium ingestion helps to maintain and restore plasma volume and osmolality by continuing thirst sensation (thus drinking) and also by increasing body fluid retention. A high sodium meal or intravascular hypertonic saline infusion may cause transient osmotically mediated blood pressure increases, but in healthy people, acute sodium ingestion does not cause sustained hypertension. The purpose of this review is to provide evidence that acute increases in sodium are an intrinsic part of the thirst response during and after exercise, and that blood pressure increases associated with hypertonicity appear to be short lived.

Drug-induced syndrome of inappropriate antidiuretic hormone

HYPONATREMIA, OFTEN DEFINED AS SERUM SODIUM LESS THAN 130 mmol/L, is the most common electrolyte disturbance among hospitalized patients. A complication of a variety of diseases, surgical treatments, or drugs, it may be hypertonic, hypotonic, or isotonic in nature. Antidiuretic hormone (ADH) is also known as arginine vasopressin (AVP). Produced in the posterior pituitary gland in response to an increased plasma sodium concentration, it induces water retention. It increases cellular permeability to water in the distal tubule and collecting duct of the nephron, leading to increased water resorption by the kidney. The syndrome of inappropriate antidiuretic hormone secretion (SIADH) is characterized by either the sustained release of ADH in the absence of stimuli, or by the enhanced action of ADH on the kidneys. Increased ADH activity impairs the kidney’s ability to dilute urine, resulting in decreased excretion of ingested water and a highly concentrated and decreased volume of urine. If fluid intake is not sufficiently reduced in the setting of increased ADH activity, serum hypotonicity and hyponatremia will occur. Patients with SIADH will present with normal volume status (euvolemic) because the excess water distributes evenly throughout the body’s fluid compartments. Causes of SIADH include malignant diseases (e.g., carcinoma, lymphomas, sarcomas), pulmonary disorders (e.g., pneumonia, asthma), central nervous system disorders (e.g., meningitis, stroke, head trauma), and a number of medications.