Excretion Of Na Research Articles

Strategies of NHX antiporters to deal with salt stress

The adverse effects of salinity on plant growth are generally associated with the low osmotic potential of the soil solution and the high level of sodium toxicity (and chlorine toxicity for some species) which cause multiple perturbations on plant metabolism, growth, and development at the molecular, biochemical and physiological levels. The vacuolar NHX and plasma membrane SOS antiporters mediate cation and proton exchange across the tonoplast and plasma membrane, respectively. The SOS transporters allow the excretion of Na+ from the cytoplasm to the outside environment and alternatively, NHXs provide Na+ transport from the cytoplasm to the vacuole. Cellular ion homeostasis is an essential phenomenon for all organisms. Most cells manage to maintain a high level of potassium and a low level of sodium in the cytoplasm through the coordination and regulation of different transporters and channels instead of the NHX-type vacuolar antiport. In this article, some important mechanisms in the regulation of ionic ions such as Na+. will be discussed.

Diuretic, Natriuretic, And Ca2+-Sparing Effect Of The Alkaloid Boldine In Rats

Abstract Background Previous studies indicate the renal vasodilating effects of boldine, an alkaloid found in Peumus boldus. However, its potential to induce diuresis still needs to be studied. Methods Wistar rats were used and the urine volume was noted for 8 h and further studied. Results The acute treatment at 0.1 and 0.3 mg/kg of boldine showed a diuretic, natriuretic, and Ca2+-sparing effect in rats without changing the urinary elimination of K+and Cl-. When boldine was given in combination with hydrochlorothiazide, there was an increase in urinary volume compared to the vehicle group. However, this was not different from the treatments in its isolated form. Urine Ca2+values ​​remained low but were not enhanced by this association. The excretion of Na+and Cl- was significantly increased compared to the group that received only vehicle or boldine. On the other hand, although the association of amiloride plus boldine did not result in a diuretic effect, the increase in Na+and the reduction in K+excretion were significantly potentiated. Furthermore, in the presence of the non-selective muscarinic receptor antagonist atropine, boldine showed reduced capacity to increase urinary volume, maintaining the natriuretic and Ca2+-sparing effect, besides a very evident K+-sparing action. Similar results were obtained in the presence of the non-selective cyclooxygenase inhibitor indomethacin. Furthermore, boldine showed an ex vivo antiurolithiasis activity, reducing calcium oxalate’s precipitation and crystallization. Conclusions This study reveals the diuretic, natriuretic, Ca2+-sparing, and antiurolithiatic effects of boldine, an action possibly related to muscarinic receptor activation and prostanoid generation.

Sodium Homeostasis, a Balance Necessary for Life.

Body sodium (Na) levels must be maintained within a narrow range for the correct functioning of the organism (Na homeostasis). Na disorders include not only elevated levels of this solute (hypernatremia), as in diabetes insipidus, but also reduced levels (hyponatremia), as in cerebral salt wasting syndrome. The balance in body Na levels therefore requires a delicate equilibrium to be maintained between the ingestion and excretion of Na. Salt (NaCl) intake is processed by receptors in the tongue and digestive system, which transmit the information to the nucleus of the solitary tract via a neural pathway (chorda tympani/vagus nerves) and to circumventricular organs, including the subfornical organ and area postrema, via a humoral pathway (blood/cerebrospinal fluid). Circuits are formed that stimulate or inhibit homeostatic Na intake involving participation of the parabrachial nucleus, pre-locus coeruleus, medial tuberomammillary nuclei, median eminence, paraventricular and supraoptic nuclei, and other structures with reward properties such as the bed nucleus of the stria terminalis, central amygdala, and ventral tegmental area. Finally, the kidney uses neural signals (e.g., renal sympathetic nerves) and vascular (e.g., renal perfusion pressure) and humoral (e.g., renin-angiotensin-aldosterone system, cardiac natriuretic peptides, antidiuretic hormone, and oxytocin) factors to promote Na excretion or retention and thereby maintain extracellular fluid volume. All these intake and excretion processes are modulated by chemical messengers, many of which (e.g., aldosterone, angiotensin II, and oxytocin) have effects that are coordinated at peripheral and central level to ensure Na homeostasis.

Structural diversity in salt excreting glands and salinity tolerance in Oryza coarctata, Sporobolus anglicus and Urochondra setulosa

Unlike the bicellular glands characteristic of all known excreting grasses, unique single-celled salt glands were discovered in the only salt tolerant species of the genus Oryza, Oryza coarctata. Salt tolerance has evolved frequently in a large number of grass lineages with distinct difference in mechanisms. Mechanisms of salt tolerance were studied in three species of grasses characterized by salt excretion: C3 wild rice species Oryza coarctata, and C4 species Sporobolus anglicus and Urochondra setulosa. The leaf anatomy and ultrastructure of salt glands, pattern of salt excretion, gas exchange, accumulation of key photosynthetic enzymes, leaf water content and osmolality, and levels of some osmolytes, were compared when grown without salt, with 200mM NaCl versus 200mM KCl. Under salt treatments, there was little effect on the capacity for CO2 assimilation, while stomatal conductance decreased with a reduction in water loss by transpiration and an increase in water use efficiency. All three species accumulate compatible solutes but with drastic differences in osmolyte composition. Having high capacity for salt excretion, they have distinct structural differences in the salt excreting machinery. S. anglicus and U. setulosa have bicellular glands while O. coarctata has unique single-celled salt glands with a partitioning membrane system that are responsible for salt excretion rather than multiple hairs as previously suggested. The features of physiological responses and salt excretion indicate similar mechanisms are involved in providing tolerance and excretion of Na+ and K+.

Effects of high salinity in drinking water on behaviors, growth, and renal electrolyte excretion in crossbred Boer goats under tropical conditions.

Background and Aim:The high salinity of drinking water has been a significant problem of the Mekong Rivers Delta. Animals drinking high salinity water altered feed and water intake (WI), urinary electrolytes excretion, and productivity. This study aimed to evaluate the effects of high salinity in drinking water on drinking and eating behaviors and kidney function in crossbred goats.Materials and Methods:The experiment was completely randomized with two treatments: freshwater (0%, seawater [SW0]) and water high in salinity (1.5%, SW1.5) from diluted SW, with five replicates (five animals per treatment). This experiment lasted 3 weeks: the 1st week for the pre-treatment period and the 2nd-3rd weeks for the post-treatment. Dry matter intake (DMI) and WI were recorded every day, while urine volume (UV) was determined from day 8 to day 21. Blood and urinary samples were collected on days 6, 14, and 21 of the study for electrolytes and creatinine analysis.Results:The results demonstrated that both DMI and WI were affected by SW1.5 (p<0.05). Goats drinking from SW1.5 had lower DMI during D19–21, and the ratio of DMI/WI was significantly different during D16–21 (p<0.05). Interestingly, the UV from SW1.5 was higher than that from SW0 during D13–21 (p<0.05). Although the body weights (BW) of both groups were similar (p>0.05), the weight gain observed in the SW1.5 group tended to decrease (p=0.056) at the 2nd week. The concentration of electrolytes in blood did not differ between the groups (p>0.05). In contrast, the concentration and excretion of Na+ and Cl- in urine increased in SW1.5 goats at D14 (p<0.05), while creatinine levels in the blood remained normal (p>0.05).Conclusion:The study concluded that crossbred male goats can tolerate 1.5% saline water from diluted SW for 2 weeks. The high salinity in water influences drinking and eating behavior in growing goats. However, the adaptive mechanism by increasing urine output and reducing the reabsorption of Na+ and Cl- in the kidney is the key function and works faster than behavioral responses. The kidney apparently drives drinking behavior during high salinity water consumption.

Contradiction between genetic analysis and diuretic loading test in type I Bartter syndrome: a case report

BackgroundIn typical cases of Bartter syndrome (BS), assessing response to diuretics (furosemide and thiazide), hereinafter referred to as diuretic loading test, may be used to diagnose the type by detecting which part of the kidney tubule is not functioning correctly. However, the diuretic loading test may not always agree with the results of genetic analyses.Case presentationA 5-year-old boy was admitted due to lower extremity weakness and abnormal gait. He had a recurrent episode of muscle weakness and laboratory results showed severe hypokalemia. The direct genomic sequencing of the case revealed a new mutation in the SLC12A1 gene, which is associated with type I Bartter syndrome. Because there was the difference between the phenotype and genotype, we conducted a diuretic loading test to confirm the diagnosis. However, the results showed a clear increase in urine excretion of Na and Cl. These results were not consistent with typical type I BS, but consistent with the patient’s phenotype.ConclusionThe diuretic loading test has limited utility for diagnosis especially in atypical cases. On the other hand, this test, which allows assessment of channel function, is useful for better understanding of the genotype-phenotype correlation.

5-Aminolevulinic Acid Improves Morphogenesis and Na+ Subcellular Distribution in the Apical Cells of Cucumis sativus L. Under Salinity Stress.

Soil salinity causes damage to plants and a reduction in output. A natural plant growth regulator, 5-aminolevulinic acid (ALA), has been shown to promote plant growth under abiotic stress conditions. In the present study, we assessed the effects of exogenously applied ALA (25 mg L−1) on the root architecture and Na+ distribution of cucumber (Cucumis sativus L.) seedlings under moderate NaCl stress (50 mmol L−1). The results showed that exogenous ALA improved root length, root volume, root surface area, and cell activity in the root tips, which were inhibited under salt stress. In addition, although salinity stress increased the subcellular Na+ contents, such as those of the cell wall, nucleus, plastid, and mitochondria, ALA treatment reduced these Na+ contents, except the soluble fraction. Molecular biological analysis revealed that ALA application upregulated both the SOS1 and HA3 transcriptional and translational levels, which suggested that the excretion of Na+ into the cytoplasm cloud was promoted by exogenous ALA. Meanwhile, exogenously applied ALA also upregulated the gene and protein expression of NHX1 and VHA-A under salinity stress, which suggested that the compartmentalization of Na+ to the vacuole was enhanced. Overall, exogenous ALA mitigated the damage caused by NaCl in cucumber by enhancing Na+ redistribution and increasing the cytoactivity of root cells.

Protective Effects of Descurainia sophia against Gentamicin Induced Nephrotoxicity in Rats.

Several studies have tried to find an efficient agent to prevent or reverse gentamicin (Gm) induced acute kidney injury (AKI). In this study, we assessed the potential renal protective effects of Descurainia sophia (L.) Webb ex Prantl against Gm-induced nephrotoxicity in rats. Thirty-five male Wistar rats were categorized in five groups (n = 7 per group). Control group was treated with normal saline. In four experimental groups, the rats were initially treated with normal saline (A), 800 (B), 1600 (C) and 2400 (D) mg/kg Descurainia sophia respectively for 28 days. After that, the rats of experimental groups were treated with Gm (80 mg/Kg) for 7 consecutive days. Blood and urine markers, as well as apoptosis and histological features were determined. Serum BUN, creatinine, cholesterol, and triglycerides level, as well as urinary excretion of Na+ significantly increased in group A. Furthermore, Gm induced inflammatory cells infiltration, apoptosis, and renal cells injuries in rats were pretreated with normal saline (group A). However, in the rats pretreated with Descurainia sophia extract (groups B, C, and D, there were significant and dose-dependent reductions in serum BUN, creatinine, cholesterol and triglyceride, urinary Na+ excretion, apoptosis rate, and inflammatory cells infiltration in renal tissues. Overall, Descurainia sophia showed significant protective effects against Gm-induced AKI by alleviating biochemical and histological markers of renal toxicity.

Abstract 16216: Increases in Renal Nkcc2 and Ncc Preceded the Elevation of Blood Pressure in Mice Treated With Clozapine

One of major side effects of clozapine, a common antipsychotic drug, is hypertension. In order to explore the pathogenesis of the drug-induced hypertension, we examined the renal sodium transport proteins and BP in the C57Bl6/J male mice treated with clozapine at different doses for 1 week. Clozapine at 20mg/kg/day via osmotic mini-pump increased SBP ( 110±0.6,mmHg, femoral artery, under anesthesia) and DBP (76.7±1) relative to vehicle (97.6±1.2/71.2±2.7) while the renal protein expression of NKCC2 (180±21, % of vehicle) and NCC (171±22), and ENaC-α (140±7), β(166±21) and γ(130±7) was increased without changes in NHE3 and α1-NKA (n=5/group). Clozapine at lower doses (5&amp;10mg/kg/day,IP) did not change the conscious SBP and DBP monitored daily by tail-cuff, even on day 7 in 5 mg/kg group (115.61±1.6/90.1±1.3) and in 10mg/kg group (116.8±2/89.0±1.6) relative to vehicle (111.9±1.5/86.9±1.4) (n=4/group). Urinary excretion of Na + &amp; K + and serum concentrations of Na + , K + , Cl - , creatinine were similar in all groups. However, renal protein expression of NKCC2 was increased in 5mg/kg (360±80, % of vehicle) and 10mg/kg (247±50) groups; NCC was increased at 5 mg/kg (175±9); α1-NKA was increased in 5mg/kg (216±5) and 10mg/kg (163±2) groups. No increases were found in the protein expression of NHE3 and ENaCs. Those increases in renal NKCC2 &amp;NCC at 5 &amp; 10 mg/kg were consistent with those at 20 mg/kg. AT1R was increased at 5 (221±20) &amp;10mg/kg (255±21) while renin (186±15) and ACE1 (186±5), not ACE2, were increased at 5 mg/kg suggesting an activation of RAAS in kidney. NOX4, not NOX2, was increased at 5 mg/kg (453±69) while NOS3, not NOS1&amp;2, was decreased at 5 (60±21) and 10mg/kg (64±5) groups. TNFα, not IL-6 was increased at 5 (222±18) &amp;10 mg/kg (321±26). In cultured mouse distal convoluted tubule cells, clozapine also increased NCC and α1-NKA at 1nM (169±4;156±7) and 10nm(175±23;183±15) respectively ( 24h,n=4/group). Those changes in kidney, including increases in sodium transport proteins, RAAS components, ROS generation enzymes, inflammation factors and decrease in NO synthase, preceded the elevation of BP suggesting that direct or indirect regulations of clozapine on those proteins may play an important role in the pathogenesis of the drug-induced hypertension.

Abstract P334: The Relationship Between Urinary Sodium-to-Potassium Ratio And High Blood Pressure: TMM CommCohort Study

Introduction: Recently, the balance between sodium and potassium intake, i.e. sodium-to-potassium (Na/K) ratio, has received significant attention for prevention of hypertension. Previous studies reported the positive association between urinary Na/K (uNa/K) ratio and hypertension. However, even the same uNa/K ratio value, there might be high Na/ high K ratio or low Na/ low K ratio. Hypothesis: We assessed the hypothesis that blood pressure (BP) is higher in high Na/ high K group than that in low Na/ low K group even at the same uNa/K ratio in general population in cross-sectional study. Methods: The subjects were 20 to 74 years old who participated in The Tohoku Medical Megabank Project Community-based Cohort Study. Of these participants, we targeted 54,011 subjects (men: 20,505 women: 33,506 mean age: 59.9 years) who had information of BP, urinary Na and K. We estimated 24-h urinary excretion of Na and K using Tanaka formula. Urinary Na and K were each classified into quartiles (Na; Q1~Q4, K; Q1~Q4), and set all 16 groups of uNa/K ratio by combining Na and K respectively. To assess the relationship between casual uNa/K ratio and BP, we performed an analysis of covariance to calculate the adjusted mean systolic BP (SBP). We included covariate factors as age, sex, BMI and alcohol intake. We also assessed the relationship between uNa/K ratio and SBP using multiple regression analyses adjusted for covariate factors. We stratified the participants into two groups: ‘under treatment for hypertension’ (n=17,091) and ‘without treatment for hypertension (n=36,920)’. Results: The mean of uNa/K ratio for each group of Na (Q1)/K(Q1), Na (Q2)/K(Q2), Na (Q3)/K(Q3) and Na (Q4)/K(Q4) was all 4.0. As previous report showed, higher uNa/K ratio group showed higher SBP and lower uNa/K group showed lower BP. When we compared adjusted mean SBP of Na (Q1)/K(Q1) and Na (Q4)/K(Q4) the value were comparable, but the value were significantly higher in Na (Q4)/K(Q4) group (The adjusted mean SBP of Na (Q1)/K(Q1), Na (Q2)/K(Q2), Na (Q3)/K(Q3) and Na (Q4)/K(Q4) was 123.6, 124.9, 124.7 and 125.5 mmHg, respectively). The uNa/K was significantly positively associated with SBP independently of age, sex, BMI, and alcohol intake. The finding was unchanged the results in under treatment group. Conclusions: BP was significantly higher in high Na/ high K group than in low Na/ low K group even at the same uNa/K ratio. We suggested that not only increasing K intake but also reducing salt is important for preventing hypertension.

Діуретична активність похідного метилксантину фуроксану за одноразового та тривалого застосування на функцію видільної системи щурів на тлі спонтанного діурезу

The study of the effect of furoxane on renal activity under conditions of spontaneous diuresis was performed by the method of Berkhin. Hydrochlorothiazide was chosen as a reference drug. Furoxane and hydrochlorothiazide were administered intragastrically at a dose of 25 mg/kg for 7 days. The content of Na+ and K+in the urine was determined by flame photometry. The concentration of creatinine in the urine was studied by the method of Folin in the modification of Berkhin. The obtained results were calculated using the methods of variation statistics. The analysis of the results shows that under one-time action of furoxane in rats the daily urination increased by 210.4 % (p &lt;0.001), the concentration of Na+ in the urine of rats increased by 51.9 % (p &lt;0.05), and the concentration of K+ in the urine tended to increase by 5.6 %. Natriuresis increased 1.7 times (p &lt;0.05), potassium - 1.23 times (p &lt;0.05). Excretion of endogenous creatinine increased 1.49 times (p &lt;0.05), indicating an improvement in glomerular ultrafiltration. After administration of hydrochlorothiazide there was an increase in diuresis by 92.2 % (p &lt;0.05), urinary Na+ concentration increased by 49% (p &lt;0.05) and increased Na+excretion from urine by 23.3 % (p &lt;0.05). K+ concentration in urine increased by 12.6 %, and K+excretion - by 27.5 % (p &lt;0.05). Thus, a single administration of furoxane at a dose of 25 mg/kg led to an increase in daily diuresis, Na+ and K+ diuresis, which indicates the potential diuretic and saluretic properties of the drug. Long-term (7 days) furoxane administration contributed to the increase of urination in animals. After 3 days diuresis increased by 226,1 % (p &lt;0.001), on 7th day – by 236,3 % (p &lt;0.001). Salures was increased: the excretion of Na+ after 3 days increased by 2.27 times (p &lt;0,05), after 7 days - by 2,38 times (p &lt;0,05), K+ - 1.83 times (p &lt;0.05). The gradual increase in creatinine excretion in the dynamics of the use of furoxane, indicated a possible prolongation of the effect of furoxane. Thus, furoxane, which by its chemical structure belongs to methylxanthine derivatives is a promising pharmacologically active substance for further study of its specific activity and safety in order to create a highly effective diuretic and implementation in clinical practice.

The discrimination of acute tubular necrosis and prerenal azotemia using two biomarkers simultaneously

Introduction: The fractional excretion of sodium (FE Na) in urine has appeared as a helpful way to distinguish prerenal azotemia from acute tubular necrosis (ATN). Objectives: The urinary index of sodium has some limits. Lithium can be an additional careful indicator. The goal of our study was to assess the standards fractional excretion of sodium and lithium, (FE Na and FE Li) in distinguishing pre-renal azotemia (PRA) from ATN. Patients and Methods: Twenty-seven patients with prerenal azotemia, 25 patients with ATN and 20 healthy persons were included in this investigation. The plasma and urine sodium, creatinine and lithium levels were assessed. Additionally, FE Na and FE Li were calculated. To assess the diagnostic usefulness of FE Na and FE Li in discriminating prerenal azotemia from ATN, we created a receiver operating characteristic (ROC) curve. Results: The area under the curves (AUCs) of fractional excretion of Li and Na were 0.84 and 0.83 for distinguishing prerenal azotemia from ATN, respectively. There was a significant direct association between FE Na and FE Li in patients with ATN (P=0.001). No significant association of FE Na and FE Li in patients with prerenal azotemia was detected (p=0.26). By a cutoff point of 2.96%, the sensitivity and specificity for FE Na, were 68% and 75%, respectively for distinguishing PRA from ATN. By a cutoff point of 4.17%, the sensitivity and specificity of FE Li were 80% and 79%, respectively, for distinguishing prerenal azotemia from ATN. Conclusion: This investigation appeared a high AUC and accuracy of fractional excretion of sodium and lithium as a diagnostic method for distinguishing prerenal azotemia from ATN when used simultaneously. However, the discrimination of sensitivity and specificity of fractional excretion of lithium was greater than the fractional excretion of Na.

Abstract 081: Ghrelin is Produced by the Kidney and Mediates Distal Tubular Sodium Reabsorption in Rats

Ghrelin is a 28-amino acid peptide hormone that exerts powerful appetite-stimulating effects. Ghrelin receptor expression has been reported in the collecting duct, but the role of ghrelin in the kidney is unknown. The present studies confirmed ghrelin mRNA expression in inner medullary collecting duct cells (N=6) using RT PCR and sequencing of the 320-bp PCR product. Ghrelin peptide expression was also confirmed in these cells using immunohistochemistry and flow cytometry. To test intrarenal ghrelin action, 12-week-old uninephrectomized female Sprague-Dawley rats (N=26) received 3 bolus injections of ghrelin siRNA (N=7) or scrambled siRNA (N=7) into the renal interstitial (RI) space of the remaining kidney, each injection 48h apart. Following the last injection, rats received three, 1h RI infusions of 5% dextrose in water. Mean arterial pressure (MAP), urine sodium (Na + ) excretion (U Na V), glomerular filtration rate (GFR), fractional excretion of Na + (FE Na ), and fractional excretion of lithium (FE Li ) were calculated. In a separate set of rats, renal blood flow (RBF) was measured for 1h (N=6 for both ghrelin siRNA and scrambled siRNA). RI ghrelin siRNA-infused rats demonstrated significantly higher U Na V compared to scrambled siRNA-infused rats for all 3 periods (0.29±0.06 vs. 0.09±0.01, 0.35±0.09 vs. 0.11±0.03, and 0.27±0.07 vs. 0.09±0.02 μmol/min; P&lt;0.01, P&lt;0.05, and P&lt;0.05 respectively) and significantly increased FE Na compared to scrambled siRNA infused rats (0.26±0.05 vs. 0.11±0.02, 0.35±0.06 vs. 0.11±0.03, and 0.24±0.04 vs. 0.10±0.03%; P&lt;0.05, P&lt;0.01, and P&lt;0.05 respectively). There were no differences in in GFR, FE Li , MAP, or RBF. Since the increase in U Na V was not accompanied by similar increases in GFR, the effect of renal ghrelin inhibition suggested a tubular rather than hemodynamic, mechanism of action. To localize the specific tubular site, events distal to the renal proximal tubule were identified by changes in FE Na that occurred independently of changes in FE Li . RI ghrelin siRNA significantly increased FE Na without altering FE Li , suggesting distal nephron-dependent Na + reabsorption. Together, these data introduce ghrelin as a novel intrarenal peptide responsible for tonic Na + reabsorption at the level of the distal nephron.

PRESCRIPTION PATTERN OF DIURETICS IN A TERTIARY CARE HOSPITAL

Diuretics are drugs that increase the rate of urine flow; clinically useful diuretics also increase the rate of excretion of Na+ (natriuresis) and an accompanying anion, usually Cl. Diuretics are a mainstay of therapy for a wide variety of diseases ranging from hypertension to the nephrotic syndrome.&#x0D; Objective: To study the prescribing patterns of diuretics in General Medicine and ICU. To assess the drug-drug interaction of diuretics. To study the route of administration of diureics. &#x0D; Materials and methods: A prospective observational study was conducted over a period of six months at general medicine and ICU department of Basaveshwara Medical College and Hospital and Research Centre, Chitradurga.a otal of 100 in-patients are included as study subject.&#x0D; Results: Mostly prescribed diuretic in this study were furosemide (52.9%), followed by mannitol (28.1%), spironolactone (11.57%), torsemide (5.79%), amiloride (0.82%) and hydrochlorothiazide (0.82%). Out of 100 prescriptions 84.4% of diuretics prescribed in intravenous route, 15.6% of diuretics prescribed in oral route. Out of 100 prescriptions total 89 drug interactions with diuretics are found. In that 2.3% major interactions and 67.4% moderate interactions and 30.3% minor interactions are found.&#x0D; Conclusion: Prescription monitoring helped to reduce the diuretic usage errors with respect to dose and drug-drug interaction with other prescribed drugs to provide better patient care.&#x0D; Keywords: prescribing pattern, drug-drug intraction, diuretics

Salt Restriction Affects the Excretions of Minerals (Na, K, Ca, Mg, P and Zn) in the Second Voided Fasting Early Morning Urine.

The plasma concentrations of mineral (sodium (Na), potassium (K), calcium (Ca), magnesium (Mg), phosphorus (P), and zinc (Zn)) are kept within narrow ranges to maintain homeostasis; hence, it is difficult to use them as indicators of nutritional status. We selected the excretion of these minerals in the second voided fasting early morning urine (EMU) as potential indicators of nutritional status. We previously reported that Na restriction caused a negative balance of Ca and Mg. Therefore, Na restriction can cause changes in EMU-minerals. This study aimed to examine the relationship between dietary Na restriction and urinary mineral excretion. The study lasted for 21 d, including 16 d of balance period and 3 d of recovery period. The participants (11 healthy young women) were divided into the Na restriction group (n=5) (NaCl: 6 g/d) and control group (n=6) (NaCl: 12 g/d). The Na restriction group changed to the control diet (NaCl: 12 g/d) during only the recovery period. The EMU-Na, Ca, Mg, P and Zn in the Na restriction group significantly decreased compared with that of the control group. The EMU-Na, K, Ca, Mg, and Zn in the group with NaCl intake of 6 g/d significantly decreased compared with that of the group with NaCl intake of 12 g/d (in the Na restriction group). We conclude that the decrease in excretion of Na, Ca, Mg and Zn in the EMU can lead to Na restriction. This result can serve as basis when considering EMU as an indicator of mineral status.

Diuretic activity and neuropharmacological effects of an ethanol extract from Senna septemtrionalis (Viv.) H.S. Irwin & Barneby (Fabaceae)

Ethnopharmacological relevance Senna septemtrionalis (Viv.) H.S. Irwin & Barneby (Fabaceae) is a shrub empirically used as diuretic, and for the treatment of neurological disorders. These pharmacological effects have not been previously evaluated. Aim of the studyTo evaluate the diuretic and CNS effects of a standardized ethanol extract of Senna septemtrionalis aerial parts (SSE). Materials and methodsGas chromatography mass spectrometry was used to perform a chemical analysis with SSE. In all tests, SSE was evaluated from 10 to 100 mg/kg p.o.The diuretic activity of SSE was assessed in mice individually placed in metabolic cages. After 6 h, the urine volume and the electrolyte excretion (Na and K) were measured. The role of prostaglandins and nitric oxide was assessed administrating mice with indomethacin and N(ω)-nitro-L-arginine methyl ester (L-NAME), prior the administration of 100 mg/kg SSE. The sedative effects of SSE were analyzed with the pentobarbital-induced sleeping time test. The effects of SSE on motor coordination in mice were evaluated with the rotarod test. The antidepressant-like activity of SSE was analyzed with the forced swimming test (FST) and the tail suspension test (TST). The role of 5-HT2 receptor, α1-and α2-adrenoceptors, or muscarinic receptors was assessed administrating mice with cyproheptadine, prazosin, yohimbine, and atropine, respectively, prior the administration of 100 mg/kg SSE in the FST. The anxiolytic-like activity of SSE (10–100 mg/kg p.o.) was assessed using the light-dark test (LDB), the elevated plus maze test (EPM), the cylinder exploratory test, and the open field test (OFT). The anticonvulsant effect of SSE (1–100 mg/kg) was evaluated in mice administered with different convulsant agents: strychnine, pentylenetetrazol (PTZ), isoniazid (INH) or yohimbine. ResultsThe main compound found in SSE was D-pinitol (42.2%). SSE (100 mg/kg) increased the urinary volume (2.67-fold), as well as the excretion of Na (5.60-fold) and K (7.2-fold). The co-administration of SSE with L-NAME or indomethacin reverted the diuretic activity shown by SSE alone. SSE lacked sedative effects and did not affect motor coordination in mice. SSE (100 mg/kg) showed higher and similar antidepressant-like effect, compared to 20 mg/kg fluoxetine, in the FST and TST, respectively. The co-administration of SSE with yohimbine reverted the antidepressant-like activity shown by SSE alone. SSE (100 mg/kg) showed anxiolytic-like activity in the four models of anxiety, with similar activity with 1.5 mg/kg clonazepam. The seizure-protective effect of SSE was ED50 = 73.9 ± 8.4 mg/kg (INH) and 40.4 ± 5.2 mg/kg (yohimbine). ConclusionThe diuretic effects of SSE involve the possible contribution of prostaglandins and nitric oxide. SSE showed moderate anxiolytic and anticonvulsant effects, whereas the participation of α2-adrenoceptors is probably associated in the antidepressant-like effects of SSE.

Electrolyte transport in the renal collecting duct and its regulation by the renin-angiotensin-aldosterone system.

Distal nephron of the kidney plays key roles in fluid volume and electrolyte homeostasis by tightly regulating reabsorption and excretion of Na+, K+, and Cl- Studies to date demonstrate the detailed electrolyte transport mechanisms in principal cells of the cortical collecting duct, and their regulation by renin-angiotensin-aldosterone system (RAAS). In recent years, however, accumulating data indicate that intercalated cells, another cell type that is present in the cortical collecting duct, also play active roles in the regulation of blood pressure. Notably, pendrin in β-intercalated cells not only controls acid/base homeostasis, but is also one of the key components controlling salt and K+ transport in distal nephron. We have recently shown that pendrin is regulated by the co-ordinated action of angiotensin II (AngII) and aldosterone, and at the downstream of AngII, mammalian target of rapamycin (mTOR) signaling regulates pendrin through inhibiting the kinase unc51-like-kinase 1 and promoting dephosphorylation of mineralocorticoid receptor (MR). In this review, we summarize recent advances in the current knowledge on the salt transport mechanisms in the cortical collecting duct, and their regulation by the RAAS.

Kolaviron mitigates proteinuria and potentiates loop diuresis in Wistar rats: Relevance to normal renal function

Aim: This study investigated the effects of oral kolaviron administration on proteinuria in Wistar rats. Methods: The study used twenty (20) Wistar rats that were divided into 4 groups of 5 rats each. Group 1 received 2 ml/kg of propylene glycol, orally, for 30 consecutive days before they were sacrificed. Groups 2, 3 and 4 received graded doses of kolaviron at 100 mg/kg, 200 mg/kg and 400 mg/kg (p.o.) respectively, for 30 consecutive days before they were also sacrificed. Results: Graded doses of kolaviron (100, 200 and 400 mg/kg p.o.) significantly lowered urine total protein and urine total protein–creatinine ratio with > 80 % reduction when compared with the control. However, creatinine clearance was significantly increased while the fractional excretions of Na+ and urea were significantly lowered. While plasma electrolytes were normal, the urinary excretion of Na+, K+ and Cl- where significantly increased in the kolaviron-treated groups. Urine output of the kolaviron-treated rats was significantly higher than that of the control without increase in both plasma and urine glucose level. Renal function biomarkers (creatinine and urea) of the rats indicated a kolaviron-enhanced improvement of renal function with an associated increase in their urine excretion. Micrographic evidence showed no apparent distortion of the kidney histoarchitecture following kolaviron administration to the rats. Conclusion: It was concluded that kolaviron mitigated proteinuria and potentiated loop diuresis in Wistar rats, a pharmacological benefit that can be utilized for the adjuvant management or treatment of proteinuria-associated nephropathies.

Two enteral solutions with different chloride concentrations administered by naso-ruminal route for fluid therapy in adult cattle

ABSTRACT: Six adult Holstein cows were used in this fluid therapy study. All animals were previously submitted to 24 hours of water and food abstaining period and submitted to both hydration treatments for eight hours in a crossover design 6x2. Two treatments with hypotonic solutions (190 mOsm/L) with low strong ion difference and different chloride concentrations solutions were executed. Physical, biochemical, blood gas analysis and urinary evaluation were executed in five different experimental times (T-24h, T0h, T4h, T8h e T24h). The hydration period caused plasmatic volume expansion. An increase in faeces humidity, excretion of Na+ and Cl- in urine, reduction of PCV, osmolarity, blood and urinary pH was observed. Both solutions can be used for fluid therapy for adult cattle and solution containing calcium chloride (SECaCl) was the most suitable for use in animals with hypochloraemia.

Triterpene derivative improves the renal function of streptozotocin-induced diabetic rats: a follow-up study on maslinic acid

Introduction: Reports indicate that oral administration of plant-derived maslinic acid (MA) exhibits hypoglycemic and renoprotective effects in streptozotocin (STZ)-induced diabetic rats. Challenges with triterpenes such as MA include low bioavailabilty which affects treatment efficacy in experimental animals. The goal of this study was to synthesize the MA derivative phenylhydrazine (PH-MA) in an effort to improve the efficacy of MA.Methods: Separate groups of non-diabetic and STZ-induced diabetic rats (n = 6) were anesthetized and the jugular vein cannulated for the infusion of 0.077 M NaCl at 9 mL/h. The bladder was catheterized for collection the urine samples every 30 min. After 30.5 h equilibration period, consecutive 30 min urine collections were made over the subsequent 4 h of 1 h control, 1.5 h treatment, and 1.5 h recovery periods. PH-MA (22 µg/h) and MA (90 µg/h) were added during the treatment periods for analysis of proximal tubular Na+ handling, plasma aldosterone and arginine vasopressin in male Sprague-Dawley rats.Results: Intravenous infusion of PH-MA (22 µg/h) and MA (90 µg/h) significantly (p ˂ .05) increased Na+ output, fractional excretion of Na+ (FENa) and lithium (FELi). Interestingly, like MA, PH-MA significantly (p ˂ .05) increased glomerular filtration rate (GFR) over the treatment period and decreased plasma aldosterone levels. Our findings indicate that PH-MA inhibited sodium reabsorption in the proximal and distal tubule as shown by increased FENa and low plasma aldosterone levels, respectively.Conclusions: PH-MA is, therefore, a promising multitarget antidiabetic agent that may ameliorate kidney function of diabetic patients at a dose four times lower than the parent compound (MA).