Plasma Sodium Concentration Research Articles

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.

Association of Cerebrospinal Fluid Biomarkers of Central Nervous System Injury With Neurocognitive and Brain Imaging Outcomes in Children Receiving Chemotherapy for Acute Lymphoblastic Leukemia

Little is known about treatment-related neurotoxic mechanisms in children with acute lymphoblastic leukemia (ALL) treated with chemotherapy only. To examine concentration of cerebrospinal fluid (CSF) biomarkers of brain injury at ALL diagnosis and during cancer therapy and to evaluate associations with long-term neurocognitive and neuroimaging outcomes and relevant genetic polymorphisms. This prospective cohort study included 235 patients with ALL who received a chemotherapy-only protocol. Patients provided CSF samples after diagnosis and throughout treatment. At 5 or more years after the diagnosis, 138 (69.7%) of 198 eligible survivors participated in long-term follow-up assessments. Children were treated from June 1, 2000, through October 31, 2010. Follow-up was completed on October 21, 2014, and data were analyzed from August 1, 2015, through September 30, 2016. Plasma concentration of high-dose intravenous methotrexate sodium and number of triple intrathecal chemotherapy injections. The CSF samples were assayed at 5 points from diagnosis to reinduction for biomarkers of myelin degradation (myelin basic protein [MBP]), neuronal damage (nerve growth factor [NGF] and total and phosphorylated tau protein), astrogliosis (glial fibrillary acidic protein [GFAP]), and neuroinflammation (chitotriosidase). DNA was genotyped for polymorphisms in drug metabolism, oxidative stress, and neurodevelopment. Leukoencephalopathy was evaluated by brain imaging. At 5 or more years after the diagnosis, survivors completed neurocognitive testing and brain imaging of white matter integrity. Among the 235 patients with CSF samples (120 boys [51.1%] and 115 girls [48.9%]; mean [SD] age at diagnosis, 6.8 [4.7] years), MBP and GFAP levels were elevated at baseline and through consolidation. The number of intrathecal injections was positively correlated with NGF level increase at consolidation (r = 0.19; P = .005). Increases in GFAP (risk ratio [RR], 1.23; 95% CI, 1.09-1.40), MBP (RR, 1.06; 95% CI, 1.01-1.11), and total tau (RR, 1.76; 95% CI, 1.11-2.78) levels were associated with a higher risk for leukoencephalopathy and higher apparent diffusion coefficient in frontal lobe white matter 5 years after diagnosis (standardized estimate, 0.05; P < .001). Increase in total tau at consolidation was associated with worse attention (omissions z score estimate, -0.20; P = .04). Glial injury may be present at diagnosis of ALL. Neuronal injury was associated with intrathecal chemotherapy. The CSF biomarkers may be useful in identifying individuals at risk for worse neurologic outcomes, particularly those with genetic susceptibility to poor brain function.

The effects of chronic acetaminophen exposure on the kidney, gill and liver in rainbow trout (Oncorhynchus mykiss)

In this study, we examined if rainbow trout chronically exposed to acetaminophen (10 and 30 μgL−1) showed histological changes that coincided with functional changes in the kidney, gill and liver. Histological changes in the kidney included movement and loss of nuclei, non-uniform nuclei size, non-uniform cytoplasmic staining, and loss of tubule integrity. Histological effects were more severe at the higher concentration and coincided with concentration dependent increases in urine flow rate and increased urinary concentrations of sodium, chloride, potassium, calcium, urea, ammonia, glucose, and protein. Yet, glomerular filtration rate was not altered with acetaminophen exposure. In the gill, filament end swelling, whole filament swelling, and swelling of the lamellae were observed in exposed fish. Lamellar spacing decreased in both exposure groups, but lamellar area decreased only with 30 μgL−1 exposure. At faster swimming speeds, oxygen consumption was limited in acetaminophen exposed fish, and critical swimming speed was also decreased in both exposure groups. The liver showed decreased perisinusoidal spaces at 10 and 30 μgL−1 acetaminophen, and decreased cytoplasmic vacuolation with 30 μgL−1 acetaminophen. A decrease in liver glycogen was also observed at 30 μgL−1. There was no change in plasma concentrations of sodium, chloride, potassium, calcium, magnesium, and glucose with exposure, suggesting compensation for urinary loss. Indeed, an increase in Na+-K+-ATPase activity in the gills was found with 30 μgL−1 acetaminophen exposure. Chronic exposure of rainbow trout to the environmentally relevant pharmaceutical acetaminophen, alters both histology and function of organs responsible for ion and nutrient homeostasis.

Effect of combinations of intravenous small-volume hypertonic sodium chloride, acetate Ringer, sodium bicarbonate, and lactate Ringer solutions along with oral fluid on the treatment of calf diarrhea

The aim of this study was to compare effect of combinations of intravenous isotonic sodium bicarbonate (NaHCO3), acetate Ringer, lactate Ringer and small-volume hypertonic sodium chloride (NaCI) solutions along with oral electrolyte solutions (OES) on the treatment of neonatal calf diarrhea with moderate dehydration and metabolic acidosis. Thirty-two calves with diarrhea were used in the study. Calves were randomly assigned to receive acetate Ringer solution (n=8), lactate Ringer solution (n=8), isotonic NaHCO3 (n=8) and 7.2% saline solutions (n=8), and two liters of OES were administrated to all calves orally at the end of intravenous administration. Blood samples for blood gas and biochemical analyses were collected at 0 hours and at 0.5, 1, 2, 4, 6 and 24 hours intervals. All the calves had mild to moderate metabolic acidosis on admission. Increased plasma volume and sodium concentration, but decreased serum total protein were observed within 0.5 hours following administration of hypertonic 7.2% NaCI + OES, compared to other 3 groups. In conclusion, administration of intravenous hypertonic 7.2% NaCI solution in small volume along with OES provided fast and effective improvement of dehydration and acid-base abnormalities within short time in treatment of calf diarrhea with moderate dehydration and metabolic acidosis.

Hypernatremia: A systems-based approach

Hypernatremia is a commonly encountered disorder in hospitalized patients in which the plasma sodium concentration exceeds 145 mM. The clinical approach to hypernatremia is often challenging for clinicians, as the underlying pathophysiology is complex and serious complications can result from its improper management. As such, the purpose of this manuscript is to provide the reader with a systematic clinical approach to the diagnosis and management of patients with hypernatremia. The following core competencies are addressed in this article: Patient care, Medical knowledge.

Ispitivanje bioekvivalencije Diklofenaka - efekti Eudragita, pripreme tableta i karakteristika formulacija na profile oslobađanja i mjere bioraspoloživosti

Objective. The study was aimed to evaluate the effects of changing excipients, including type of Eudragit polymer, on release and absorption profiles in vitro and in vivo, of tablets containing the antiinflammatory drug, diclofenac sodium. Methods. Formulation 1 consisted of diclofenac sodium tablets containing Eudragit L30, and Formulation 2 consisted of diclofenac sodium tablets containing Eudragit L100, and both formulations contained different excipients. Tablets were assessed, in vitro, for weight, hardness, diameter, thickness, mass uniformity, disintegration and dissolution profiles and drug content. Tablets were also assessed in vivo by gavage in healthy rabbits and assessing diclofenac sodium plasma concentrations and pharmacokinetic parameters. Results. Results showed that in vitro analyses demonstrated non-equivalence while in vivo analyses demonstrated equivalence. This suggests that although different types of Eudragit and excipients modulated the in vitro dissolution and release profiles of diclofenac sodium, in vivo absorption in rabbits remained similar representing bioequivalence. Conclusion. It is needed to conduct evaluations of bioequivalence of diclofenac sodium oral preparations at both in vitro and in vivo conditions.

Ontogeny-related pharmacogene changes in the pediatric liver transcriptome.

The majority of drug dosing studies are based on adult populations, with modification of the dosing for children based on size and weight. This rudimentary approach for drug dosing children is limited, as biologically a child can differ from an adult in far more aspects than just size and weight. Specifically, understanding the ontogeny of childhood liver development is critical in dosing drugs that are metabolized through the liver, as the rate of metabolism determines the duration and intensity of a drug's pharmacologic action. Therefore, we set out to determine pharmacogenes that change over childhood development, followed by a secondary agnostic analysis, assessing changes transcriptome wide. A total of 47 human liver tissue samples, with between 10 and 13 samples in four age groups spanning childhood development, underwent pair-end sequencing. Kruskal-Wallis and Spearman's rank correlation tests were used to determine the association of gene expression levels with age. Gene set analysis based on the pathways in KEGG utilized the gamma method. Correction for multiple testing was completed using q-values. We found evidence for increased expression of 'very important pharmacogenes', for example, coagulation factor V (F5) (P=6.7×10(-7)), angiotensin I converting enzyme (ACE) (P=6.4×10(-3)), and solute carrier family 22 member 1 (SLC22A1) (P=7.0×10(-5)) over childhood development. In contrast, we observed a significant decrease in expression of two alternative CYP3A7 transcripts (P=1.5×10(-5) and 3.0×10(-5)) over development. The analysis of genome-wide changes detected transcripts in the following genes with significant changes in mRNA expression (P<1×10(-9) with false discovery rate<5×0(-5)): ADCY1, PTPRD, CNDP1, DCAF12L1 and HIP1. Gene set analysis determined ontogeny-related transcriptomic changes in the renin-angiotensin pathway (P<0.002), with lower expression of the pathway, in general, observed in liver samples from younger participants. Considering that the renin-angiotensin pathway plays a central role in blood pressure and plasma sodium concentration, and our observation that ACE and PTPRD expression increased over the spectrum of childhood development, this finding could potentially impact the dosing of an entire class of drugs known as ACE-inhibitors in pediatric patients.

Extracellular volume depletion and resultant hypotonic hyponatremia: A novel translational approach

Although several methods currently exist to determine that a person is hypovolemic, it often remains very challenging to accurately estimate the effective circulating volume or amount of intravascular volume depletion in a non-controlled setting. This depletion of intravascular volume can have many causes and is frequently accompanied by hypotonic hyponatremia as a result of hypovolemia-induced release of arginine vasopressin (AVP) from the posterior pituitary gland. Here, we derive a novel, comprehensible equation that provides a theoretical insight into the complex interrelationship between the degree of isotonic volume depletion and the resultant change in plasma sodium concentration. We believe that the presented model can prove to be a valuable tool for the analysis of fluid and electrolyte imbalances.

Outcomes in Severe Hyponatremia Treated With and Without Desmopressin

BackgroundOvercorrection of plasma sodium in severe hyponatremia is associated with osmotic demyelination syndrome. Desmopressin (DDAVP) can prevent overcorrection of plasma sodium in hyponatremia. The objective of this study was to compare outcomes in hyponatremia according to DDAVP usage. MethodsThis was a retrospective observational study including all admissions to internal medicine with hyponatremia (plasma sodium concentration <123 mEq/L) from 2004 to 2014 at 2 academic hospitals in Toronto, Canada. The primary outcome was safe sodium correction (≤12 mEq/L in any 24-hour and ≤18 mEq/L in any 48-hour period). ResultsWe identified 1450 admissions with severe hyponatremia; DDAVP was administered in 254 (17.5%). Although DDAVP reduced the rate of change of plasma sodium, fewer patients in the DDAVP group achieved safe correction (174 of 251 [69.3%] vs 970 of 1164 [83.3%]); this result was driven largely by overcorrection occurring before DDAVP administration in the rescue group. Among patients receiving DDAVP, most received it according to a reactive strategy, whereby DDAVP was given after a change in plasma sodium within correction limits (174 of 254 [68.5%]). Suspected osmotic demyelination syndrome was identified in 4 of 1450 admissions (0.28%). There was lower mortality in the DDAVP group (3.9% vs 9.4%), although this is likely affected by confounding. Length of stay in hospital was longer in those who received DDAVP according to a proactive strategy. ConclusionsAlthough observational, these data support a reactive strategy for using DDAVP in patients at average risk of osmotic demyelination syndrome, as well as a more stringent plasma sodium correction limit of 8 mEq/L in any 24-hour period for high-risk patients. Further studies are urgently needed on DDAVP use in treating hyponatremia.

Vitamin E (α tocopherol) attenuates toxicity and oxidative stress induced by aflatoxin in rats.

Aflatoxins are toxic metabolites produced by Aspergillus flavus and Aspergillus parasiticus and are classified as group I carcinogens by the International Agency for Research on Cancer (IARC). The purpose of this study was to investigate the possible preventive role of vitamin E (Vit E) on aflatoxin (AF) induced toxicity by using biochemical and histopathological approaches. Wistar-Albino rats were divided into 4 groups as follows: control group, Vit E group (Vit E was administered), AFB1 group (a single dose of AFB1 was administered), AF + Vit E group (AF and Vit E were administered). The effects of Vit E on AFB1 induced tissue toxicity were evaluated by using malondialdehyde (MDA), reduced glutathione (GSH) levels, antioxidant enzyme activities, and histopathological examination in tissues. AF caused the oxidative stress by the increased MDA level and the reduced GSH level, glutathioneS-transferase (GST), catalase (CAT), glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), and glucose-6-phosphate dehydrogenase (G6PD) activities in tissues. Plasma aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH) activities, creatinine, and urea concentrations significantly increased; whereas, chloride, phosphorus, and magnesium concentrations were insignificantly affected. Plasma glucose, protein and sodium concentrations significantly decreased. Administration of AF caused hepatotoxicity, cardiotoxicity, and nephrotoxicity. As far as histopathological changes are concerned, a statistically significant difference was found in AFB1 group compared to the control group. Vit E considerably reduced plasma AST, ALT, ALP, LDH activities, and urea concentration and ameliorated the deleterious effects of AF on oxidative stress markers and pathological changes. This data indicated that the natural antioxidant Vit E might have a protective effect against AF-induced toxicity and oxidative stress.

PP.07.16] RELATIONSHIP BETWEEN PLASMA RENIN ACTIVITY, PLASMA ALDOSTERONE AND SELECTED ASYMPTOMATIC ORGAN DAMAGE INDICES IN ESSENTIAL ARTERIAL HYPERTENSION

Objective: To assess the relationship between plasma renin activity (PRA), serum aldosterone concentration (ALDO) and selected asymptomatic organ damage (AOD) indices in mild primary arterial hypertension (AH).Design and method: In 122 patients (61 men and 61 women) with untreated essential AH stage 1 (140/90 > BP < 160/100 mm Hg) and age 30–75 years we measured PRA, ALDO, and selected AOD indices (left ventricular mass index, carotid artery intima media thickness, carotid-femoral pulse wave velocity (cfPWV), central aortic pulse pressure (cPP), estimated glomerular filtration rate (eGFR)). Although the study group included only patients with mild essential AH without typical indications to perform screening for primary aldosteronism we decided to exclude patients with an aldosterone-to-renin ratio (ARR) >100 ng/dl/ng/ml/h and aldosterone concentration >15 ng/dl. Results: Based on PRA results, patients were divided into two subgroups, “low-renin” and “high-renin”, according to the Laragh and Alderman criteria (low-renin: PRA < 0.65 ng/ml/h, high-renin: PRA > 0.65 ng/ml/h). Patients with high PRA (>0.65 ng/ml/h) were characterized by lower plasma sodium concentration, several times lower aldosterone-to-renin ratio (ARR), higher ALDO, but similar level of AOD indices compared to patients with low PRA. Among AOD indices, cfPWV (p = 0.04) and cPP (p = 0.019) increased with ARR, while eGFR decreased with ALDO (p = 0.008). After adjusting for age, sex, and BMI, only eGFR was significantly correlated with ALDO (Table 1). In subjects with simultaneously high PRA and ARR values, we found significantly higher cfPWV (p = 0.02) and cPP (p = 0.04) and lower eGFR (p = 0.02) than in those with high PRA but low ARR values. Conclusions: In mild hypertension, assessment of RAAS influence on AOD should include the reciprocal relationship between renin and aldosterone. PRA itself has no predictive value for AOD. More advanced arterial stiffness and renal impairment are associated with increased PRA and ARR. RAAS activity might be useful in AOD prediction and hypertension severity assessment.

Vasopressin Receptor Antagonists in Hyponatremia: Uses and Misuses.

Decreases in the concentration of sodium in plasma constitute hyponatremia, the commonest electrolyte disorder in clinical medicine. It is now well established that its presence conveys an increased mortality risk even when the decrement is mild. In addition, recent evidence suggests that chronic and apparently asymptomatic hyponatremia is associated with increased morbidity including neurocognitive deficits and bone fractures. Furthermore, hyponatremia is associated with higher health care-related expenses. Consequently, exploring new therapeutic strategies that increase plasma sodium in a safe and effective manner is of paramount importance. In this regard, there are scant data to support the use of traditional management strategies for hyponatremia (fluid restriction, salt tablets, loop diuretics, and normal saline). Furthermore, data from a large hyponatremia registry reveal the limited efficacy of these therapies. More recently vasopressin receptor antagonists provide a promising treatment for hyponatremia by targeting its most common mechanism, namely, increased vasopressin activity. However, uncertainty still lingers as to the optimal indications for the use of vasopressin receptor antagonists in hyponatremia and a few reports have described complications resulting from their misuse. This review summarizes the appropriate and inappropriate uses of vasopressin receptor antagonists in the treatment of hyponatremia.

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.

Clinical signs, profound acidemia, hypoglycemia, and hypernatremia are predictive of mortality in 1,400 critically ill neonatal calves with diarrhea.

Profound acidemia impairs cellular and organ function and consequently should be associated with an increased risk of mortality in critically ill humans and animals. Neonatal diarrhea in calves can result in potentially serious metabolic derangements including profound acidemia due to strong ion (metabolic) acidosis, hyper-D-lactatemia, hyper-L-lactatemia, azotemia, hypoglycemia, hyperkalemia and hyponatremia. The aim of this retrospective study was to assess the prognostic relevance of clinical and laboratory findings in 1,400 critically ill neonatal calves with diarrhea admitted to a veterinary teaching hospital. The mortality rate was 22%. Classification tree analysis indicated that mortality was associated with clinical signs of neurologic disease, abdominal emergencies, cachexia, orthopedic problems such as septic arthritis, and profound acidemia (jugular venous blood pH < 6.85). When exclusively considering laboratory parameters, classification tree analysis identified plasma glucose concentrations < 3.2 mmol/L, plasma sodium concentrations ≥ 151 mmol/L, serum GGT activity < 31 U/L and a thrombocyte count < 535 G/L as predictors of mortality. However, multivariable logistic regression models based on these laboratory parameters did not have a sufficiently high enough sensitivity (59%) and specificity (79%) to reliably predict treatment outcome. The sensitivity and specificity of jugular venous blood pH < 6.85 were 11% and 97%, respectively, for predicting non-survival in this study population. We conclude that laboratory values (except jugular venous blood pH < 6.85) are of limited value for predicting outcome in critically ill neonatal calves with diarrhea. In contrast, the presence of specific clinical abnormalities provides valuable prognostic information.

Effects of acclimation to seawater salinity on some blood parameters in wild Caspian brown trout, Salmo trutta caspius

In the present study, some hematological indices were assayed after salinity challenge in smolts obtained from wild populations of Caspian brown trout. The experiment was designed into three treatments and one control group containing 90 fish per treatment. In experimental treatment, fish were exposed to salinity challenge (12 mg/l salinity) for 48 h. Fish of control group were not challenged and held in freshwater with 0.37 g/l salinity. After salinity challenge in seawater, the higher values of plasma cortisol and glucose were found in fish acclimated to seawater compared to control group (P 0.05). Plasma potassium and sodium concentrations were statistically similar between experimental groups and control group (P > 0.05). Also, plasma protein levels were lower in fish exposed to salinity challenge compared to control (P 0.05). In conclusion, the results of the present study confirm the ability of the Caspian brown trout smolts in controlling osmoregulation by alternation of some hematological parameters.

Hyponatremia: Differential Diagnosis and Treatment

Hyponatremia is the most common electrolyte abnormality seen in hospitalized patients, with up to 30 % having a plasma sodium concentration below 135 mmol/l. It is now clear that the clinical problem extends beyond the neurological symptoms, which can be explained by intracerebral osmotic fluid shifts and brain edema. Instead, chronic hyponatremia is associated with impaired gait stability and an increased risk of bone fragility fractures. Moreover, hyponatremia has been demonstrated to be an indicator of poor prognosis in a variety of conditions.Hyponatremia can be a life-threatening disorder due to increased intracranial pressure, thus requiring prompt and efficacious treatment. However, overly rapid correction may be complicated by osmotic demyelination syndrome with catastrophic clinical sequelae, i. e., spastic quadriparesis, or even coma or death.To avoid inappropriate treatment, the underlying pathophysiology in each case as well as the time course (acute vs. chronic) and the clinical and biochemical severity must be considered.The purpose of this review is to provide the reader with a systematic approach to the correct diagnosis and management of hyponatremia based on available European and international guidelines.

Renin-angiotensin-aldosterone (RAAS): The ubiquitous system for homeostasis and pathologies

Renin-angiotensin-aldosterone system (RAAS) is a vital system of human body, as it maintains plasma sodium concentration, arterial blood pressure and extracellular volume. Kidney-secreted renin enzyme acts on its substrate to form angiotensin II, a versatile effector peptide hormone. Every organ is affected by RAAS activation and the resultant hypertension, cell proliferation, inflammation, and fibrosis. The imbalance of renin and angiotensin II can result in an overwhelming number of chronic and acute diseases. RAAS is influenced by other enzymes, hormones, pumps and signaling pathways, hence, this review discusses important facets of this system, its crosstalk with other crucial factors like estrogen, thyroid, cortisol, kallikrein-kinin system, Wnt/β-catenin signaling, and sodium-potassium pump. The nexus of RAAS with the above-discussed systems was scantily explored before. So, this review furnishes a new perspective in comprehension of inflammation diseases. It is followed by the formulation of hypotheses, which can contribute to better management of an array of pathologies plaguing mankind. Manipulation of RAAS, by bending it towards ACE2 expression can regulate endocrine functions, which can be critical for a number of pathological management. Dietary intervention can restore RAAS to normalcy.

Neuronal circuits involved in osmotic challenges.

The maintenance of plasma sodium concentration within a narrow limit is crucial to life. When it differs from normal physiological patterns, several mechanisms are activated in order to restore body fluid homeostasis. Such mechanisms may be vegetative and/or behavioral, and several regions of the central nervous system (CNS) are involved in their triggering. Some of these are responsible for sensory pathways that perceive a disturbance of the body fluid homeostasis and transmit information to other regions. These regions, in turn, initiate adequate adjustments in order to restore homeostasis. The main cardiovascular and autonomic responses to a change in plasma sodium concentration are: i) changes in arterial blood pressure and heart rate; ii) changes in sympathetic activity to the renal system in order to ensure adequate renal sodium excretion/absorption, and iii) the secretion of compounds involved in sodium ion homeostasis (ANP, Ang-II, and ADH, for example). Due to their cardiovascular effects, hypertonic saline solutions have been used to promote resuscitation in hemorrhagic patients, thereby increasing survival rates following trauma. In the present review, we expose and discuss the role of several CNS regions involved in body fluid homeostasis and the effects of acute and chronic hyperosmotic challenges.

Effect of electrolyte supplementation on electrolyte profile in Marwari horses during 20 km moderate intensity riding exercise

The effect of electrolyte supplementation on plasma electrolyte profile in horses in hot environmental conditions was studied using sweat loss and sweat electrolyte concentration. Eleven adult Marwari mares were selected for the study. To develop an electrolyte supplement, 7 mares were given a preliminary 20 km moderate intensity exercise and the electrolyte supplement was designed on basis of their body weight loss and sweat electrolyte concentration during exercise. In the subsequent trials, 4 mares were kept in an exercise control group that did not receive the supplement (ECG), while 3 mares were kept in the exercise supplementation group (ESG) that received the supplement. Four other mares were used as resting controls (RG). ESG mares were daily fed 50 g electrolyte supplement and 150 g supplement orally 1 h before the 20 km trial. Mares of ESG and ECG groups were conferred 3 km trot + canter riding every day in the morning and a 20 km trot + canter ride on every 10th day of the total trial period of 40 days. Blood analysis revealed a significant (P&lt;0.05) decline in plasma calcium and chloride concentrations immediately after exercise in both groups. There was significant less post-exercise decrease of plasma calcium and chloride concentration in ESG mares. Post-exercise plasma sodium concentration was higher (P&lt;0.05) and plasma potassium concentration was lower only in ESG mares (P&lt;0.05) compared to pre-exercise concentrations. The supplement did not affect the physiological responses (heart rate and rectal temperature). However, the changes in plasma sodium, potassium, calcium and chloride concentration were in favour of better performance in supplemented (ESG) mares and advocate sweat-developed electrolyte supplementation in riding mares.

Effects of drinking saline water on food and water intake, blood and urine electrolytes and biochemical and haematological parameters in goats: a preliminary study

Drinking-water availability, both of quantity and quality, critically limits animal farming in semiarid and arid areas, but differences among species exist. The aim of the present study was to investigate goat saline-water tolerance. A group of four castrated adult males were used in a 4-week experimental period, which followed a 2-week pre-trial period and preceded a 1-week post-trial period. Animals were offered alfalfa hay and concentrates at about maintenance level and were allowed consecutively the following five levels of water salinity: 0‰, 0.5‰, 5‰, 10‰ and 20‰ NaCl. Feed and water consumption were recorded daily during trial, while blood- and urine-sample collections were performed weekly. Plasma concentrations of aldosterone, sodium (Na), potassium (K), glucose, creatinine, urea and proteins, and haematological parameters were analysed. Furthermore, urine pH, specific weight and concentrations of Na, K and creatinine were measured, as well as plasma and urine osmolality. Water intake increased until 10‰ NaCl (from 2.0 to 3.2 L/day, P &lt; 0.001) and decreased thereafter to reach 2.5 L/day. Feed intake decreased (from 1.4 to 1.1 kg/day, P &lt; 0.001) and urine excretion increased with an increasing salinity (from 1.12 to 1.47 L/day, P &lt; 0.001). Increasing salinity elevated plasma concentrations of Na (from 143 to 150 mmol/L, P &lt; 0.05), glucose (from 67.50 to 80.75 mg/dL, P &lt; 0.05), urea (from 26.5 to 47 mg/dL, P &lt; 0.01), proteins (from 6.3 to 8.3 g/dL, P &lt; 0.001), osmolality (from 284 to 299 mosm/kg, P &lt; 0.01) and creatinine (from 0.8 to 1.0 mg/dL, P &lt; 0.01) whereas, K, aldosterone and bodyweight remained unaffected. Moreover, urine osmolality (from 317 to 1217 mosm/kg, P &lt; 0.001), specific weight (from 1018 to 1040, P &lt; 0.01), Na (from 55 to 377 mmol/L, P &lt; 0.001) and K (from 144 to 329 mmol/L, P &lt; 0.001) increased, whereas, pH and creatinine were unaffected. Observed changes in other haematological parameters are considered of minor physiological importance. The results indicated that goats can subsist on drinking saline water (up to 20‰ NaCl), for at least 2 weeks without harmful effects.