Reabsorption Of Sodium Ions Research Articles

Hyaluronan Fragments Induce Lung Alveolar Edema by Activating Calcium-Sensing Receptor

One of the hallmarks of lung injury is the breakdown of the cell matrix hygroscopic high molecular weight hyaluronan (HMW-HA >106 kD) into smaller fragments of low molecular weight (LMW-HA < 500 kD) which mediate the onset and progression of acute lung injury. We have found that instillation of very low dose (1μg) of LMW-HA to wt. C57/bl6 mice was suffcient to inhibit lung epithelial ions and water transport and cause lung edema assessed by measuring lungs wet/dry ratio. LMW-HA IC50 for the induction of lung edema, the inhibition of alveolar fluid clearance (AFC) and epithelial sodium channels (ENaC) in alveolar epithelial cells, AEC1 and AEC2, in-situ, in freshly cut lung slices, was 120 nM. We found the expression of calcium-sensing receptor (CaSR), a C class G-protein coupled receptor, was activated by LMW-HA. CD44 is known to be the main membrane receptor of hyaluronan expressed by most cells including lung alveolar epithelial cells, however, because it lacks the intrinsic kinase activity necessary for the transduction of extracellular signal carried by LMW-HA, we hypothesized that it cooperated with CaSR to transduce LMW-HA injurious signal and activated intracellular signaling cascades that induced lung edema by inhibiting ENaC and AFC at 24 h. These effects were prevented by NPS2143 (1 μM), a CaSR inhibitor or calcilytic, instilled 6 h post LMW-HA, and were absent in CD44 knockout mouse. The lack of an effect on W/D ratio, AFC, or ENaC in CD44−/− mouse is evidence that LMW-HA does not directly interact with CaSR, but rather activates CD44 which cooperate with CaSR to trigger intracellular signaling cascades that cause the observed effects. Four hours post mouse airway epithelial cells confluent monolayers were incubated with 1 μg LMW-HA, CaSR expression was increased 4-fold, while amiloride sensitive short-circuit current and αβγ-ENaC subunits expression, at the apical membranes, were significantly reduced. These effects were prevented when CaSR, PLC, or PKC were inhibited with 1 μM NPS2143, 10 μM U73122, or 100 μM Rottlerin, applied 4 h prior to cells incubation with 1 μg LMW-HA, respectively. Our data show that the deleterious effect of LMW-HA on ENaC are mediated by intricate interactions between CD44-LMW-HA complex with CaSR in lung alveolar epithelial cells. The use of calcilytics to decouple the molecular complex formed by CD44-LMW-HA and CaSR may prove to be effective in restoring alveolar sodium ion reabsorption required for lung edema clearance. Department of Anesthesiology and Perioperative Medicine. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Proteolytic Activation of the Epithelial Sodium Channel (ENaC): Its Mechanisms and Implications.

Epithelial sodium channel (ENaC) are integral to maintaining salt and water homeostasis in various biological tissues, including the kidney, lung, and colon. They enable the selective reabsorption of sodium ions, which is a process critical for controlling blood pressure, electrolyte balance, and overall fluid volume. ENaC activity is finely controlled through proteolytic activation, a process wherein specific enzymes, or proteases, cleave ENaC subunits, resulting in channel activation and increased sodium reabsorption. This regulatory mechanism plays a pivotal role in adapting sodium transport to different physiological conditions. In this review article, we provide an in-depth exploration of the role of proteolytic activation in regulating ENaC activity. We elucidate the involvement of various proteases, including furin-like convertases, cysteine, and serine proteases, and detail the precise cleavage sites and regulatory mechanisms underlying ENaC activation by these proteases. We also discuss the physiological implications of proteolytic ENaC activation, focusing on its involvement in blood pressure regulation, pulmonary function, and intestinal sodium absorption. Understanding the mechanisms and consequences of ENaC proteolytic activation provides valuable insights into the pathophysiology of various diseases, including hypertension, pulmonary disorders, and various gastrointestinal conditions. Moreover, we discuss the potential therapeutic avenues that emerge from understanding these mechanisms, offering new possibilities for managing diseases associated with ENaC dysfunction. In summary, this review provides a comprehensive discussion of the intricate interplay between proteases and ENaC, emphasizing the significance of proteolytic activation in maintaining sodium and fluid balance in both health and disease.

Effect of water diuresis with hydrogen saturation on the course of acute kidney damage during the separation of oxidation and phosphorylation

Molecular hydrogen has the ability to penetrate cells, easily reach mitochondria, overcome body barriers, penetrate areas of ischemia, edema and inflammation, improve energy supply by supplying additional electrons and have antioxidant and anti-inflammatory effects by neutralizing highly reactive hydroxyl radical and peroxynitrite. In this experiment, we included 60 nonlinear male rats weighing 0.16-0.18 kg and investigated the effect of a negative redox potential solution -297.3±5.27 mV with a molecular hydrogen saturation of 1.2 ppm on the functional-biochemical processes of the kidneys in tissue hypoxia in moderately resistant rats during the separation of oxidation and phosphorylation with the introduction of 2,4-dinitrophenol at a dose of 3 mg/kg. All studies were performed on moderately stable rats. Experimental, functional, biochemical, enzyme-linked immunosorbent, physicochemical, histoenzymochemical, and statistical research methods were used. Under conditions of renal hypoxia in the separation of oxidation and phosphorylation, the use of a solution of negative redox reabsorption of sodium ions in the distal nephron reduces the manifestations of tubular proteinuria, increases the activity of succinate dehydrogenase in the proximal nephron and reduces the redox potential of urine to negative values. Negative redox potential solution with molecular hydrogen saturation has a protective effect on the kidneys and reduces elevated levels of proinflammatory cytokines of tumor necrosis factor-α, interleukin-1-β, and interleukin-6 in blood plasma, and causes oxidative modification of proteins in the renal cortex for their hypoxia in the separation of oxidation and phosphorylation.

Influence of water of negative oxidation-reduction potential with hydrogen saturation on kidney function in rats

Objective. To study the effect of water load of negative redox potential with hydrogen saturation on renal function in comparison with induced diuresis with water of negative redox potential without hydrogen saturation.Material and methods. In experiments on 60 male white-nonlinear rats weighing 0.16-0.18 kg, the effect of loading with ordinary tap water (redox potential 90.4 ± 1.45 mV), water of negative redox potential without saturation with hydrogen (redox potential - 304.5 ± 4.79 mV) and water of negative redox potential with hydrogen saturation 1.0 - 1.2 ppm and redox potential -297.3 ± 5.27 mV. Used: experimental, physiological, biochemical, chemical, physicochemical, statistical research methods.Results. Under water load of negative redox potential with hydrogen saturation in comparison with induced diuresis of negative redox potential with the use of microhydrin, there was no inhibition of glomerular filtration, filtration fraction and proximal reabsorption of sodium ions, change restorative potential of urine. These changes are explained by the lack of activation of the dysregulatory mechanism of basal vascular tone of the renal cortex under conditions of water load of negative redox potential with hydrogen saturation.Conclusion. Water loading of negative redox potential with hydrogen saturation in comparison with induced diuresis of negative redox potential without hydrogen saturation causes recovery of glomerular filtration rate, filtration fraction and proximal reabsorption of sodium ions, due to the lack of activation of the mechanism of basal vascular tone of the renal cortical substance, due to the high permeability of molecular hydrogen and uniform delivery of electrons to all organs and tissues.

Enzym konwertujący angiotensynę 2 (ACE2) – główny receptor dla wirusa SARS-CoV-2

The renin-angiotensin-aldosterone system (RAS) plays a significant role in the regulation of the water and electrolyte balance. Renin from the kidneys converts angiotensinogen to angiotensin I. Angiotensin converting enzyme (ACE) catalyzes the conversion of angiotensin I to angiotensin II. The activation of AT1 receptors by angiotensin II causes vasoconstriction, an increase in aldosterone secretion, and an increase in the reabsorption of sodium ions in nephrons, leading to elevation of the blood pressure. Angiotensin II promotes oxidative stress, growth and proliferation of cells, stimulates coagulation, inhibits fibrinolysis, and intensifies inflammatory processes. The ACE-angiotensin II-AT1R pathway is balanced by angiotensin converting enzyme 2 (ACE2), which degrades angiotensin I to angiotensin (1-9) and angiotensin II to angiotensin (1-7). Angiotensin (1-7) and angiotensin (1-9) pathways exert protective effects by activating, respectively Mas and AT2 receptors. ACE and ACE2 also have intimate roles with the plasma kallikrein-kinin system (KKS), a hormonal pathway that modulates the intrinsic blood coagulation system, endothelial cell growth and angiogenesis, the complement pathway and RAS. The appearance in Wuhan, China, of the first cases of SARS-CoV-2 infections at the end of 2019 launched a series of intensive studies, which proved that the virus invades host cells using ACE2 as a specific receptor. This survey presents basic information on the structure and tissue distribution of ACE2 and the role this enzyme plays in pathogenesis of COVID-19. A particular emphasis is given to pathophysiological effects of the functional superiority of the ACE → angiotensin II → AT1 receptor axis over the pathway ACE2 → angiotensin II → angiotensin (1-7) → Mas receptor. Such disharmony is a consequence of SARS-CoV-2 induced ACE2-downregulation. In the era of the expanding COVID-19 pandemic, intensive research is conducted not only on vaccines and antiviral drugs, but also on compounds that can restore the functional balance between angiotensin II and angiotensin (1-7). © 2021 Polish Pharmaceutical Society. All rights reserved.

The Preventive Effect of Cardiac Sympathetic Denervation Induced by 6-OHDA on Myocardial Ischemia-Reperfusion Injury: The Changes of lncRNA/circRNAs-miRNA-mRNA Network of the Upper Thoracic Spinal Cord in Rats.

In this study, we investigated whether chemical 6-hydroxydopamine (6-OHDA) stimuli caused cardiac sympathetic denervation (SD), and we analyzed gene expression profiles to determine the changes in the lncRNA/circRNAs-miRNA-mRNA network in the affected spinal cord segments to identify putative target genes and molecular pathways in rats with myocardial ischemia–reperfusion injury (MIRI). Our results showed that cardiac sympathetic denervation induced by 6-OHDA alleviated MIRI. Compared with the ischemia reperfusion (IR, MIRI model) group, there were 148 upregulated and 51 downregulated mRNAs, 165 upregulated and 168 downregulated lncRNAs, 70 upregulated and 52 downregulated circRNAs, and 12 upregulated and 11 downregulated miRNAs in the upper thoracic spinal cord of the SD-IR group. Furthermore, we found that the differential genes related to cellular components were mainly enriched in extracellular and cortical cytoskeleton, and molecular functions were mainly enriched in chemokine activity. Pathway analysis showed that the differentially expressed genes were mainly related to the interaction of cytokines and cytokine receptors, sodium ion reabsorption, cysteine and methionine metabolism, mucoglycan biosynthesis, cGMP-PKG signaling pathway, and MAPK signaling pathway. In conclusion, the lncRNA/circRNAs-miRNA-mRNA networks in the upper thoracic spinal cord play an important role in the preventive effect of cardiac sympathetic denervation induced by 6-OHDA on MIRI, which offers new insights into the pathogenesis of MIRI and provides new targets for MIRI.

Influence of negative redox potential on functional and biochemical processes of the kidneys at the polyuric stage of sublimate nephropathy

Goal. To find out the effect of water load of negative redox potential on the functional and biochemical processes of the kidneys in comparison with induced diuresis with ordinary tap water at the poliuric stage of sublimate nephropathy in hyponatric diets.Materials and methods. In experiments on 60 white non-linear mature male rats in a hyposodium diet at the poliuric stage of sublimate nephropathy 72 hours after subcutaneous administration of sublimate at a dose of 5mg/kg per load of water with a negative redox potential (-232.0±25.12 mV) compared to induced diuresis with ordinary tap water (redox potential 88.7±18.35 mV), which ORP-meter was measured, lipid peroxidation, tissue fibrinolysis, succinate dehydrogenase activity, β-2-microglobulin reabsorption, excretory, ionoregulatory functions were studied, glomerular-tubular and tubular-tubular balance of the kidneys.Results and discussion. According to the experience installed protective, antioxidant effects of water negative redox potential, which was manifested by the decrease in the level of diene conjugates, malonic aldehyde, the degree of swelling and damage by the ratio of K+/Na+ to the cortical substance of the kidney, improve the reabsorption of sodium ions, β-2-microglobulin in the proximal tubules with a reduction in the loss of this cation from urine by increasing the supply of electrons to the tubules of the kidneys. Improving the energy status of the proximal nephron in conditions experience increased activity of succinate dehydrogenase in the cortical portion of the kidney has led to the improvement of tissue fibrinolysis and processes glomerular-tubular and tubular-tubular balance with loss correlations, the relative water reabsorption from the glomerular filtration, absolute proximal and distal reabsorbtion of sodium ions.

PECULIAIRITIES OF THE FUNCTIONING CIRCADIAN ORGANIZATION THE ION-REGULATING FUNCTION OF KIDNEY UNDER THE CONDITION OF PINEAL GLAND HYPERFUNCTION OF THE INFLUENCE NITROGEN MONOXIDE SYNTHESIS BLOCKADE

The aim of our work was to investigate the peculiarities of the functioning circadian organization the ion-regulating function of pineal gland hyperfunction of the influence nitrogen monoxide synthesis blockade. Materials and methods: The experiments were conducted on 72 mature non-linear albino male rats with their body mass 0,15-0,18 kg. The control group included animals (n=36) kept under conditions of usual light regimen (12.00L:12.00D) during 7 days. The experimental group included animals (n=36) injected with N-nitro-L-arginine (L-NNA) in the dose of 20 mg/kg during 7 days under conditions of continuous absolute darkness (12.00D:12.00D). On the 8th day the animals were exposed to 5% water load with heated to room temperature water supplied and the parameters of the kidney ion-regulating function under conditions of forced diuresis were investigated. Results and conclusions: The obtained results of the performed blockade nitrogen monoxide (NO) synthesis in conditions of hyperfunction of the brain epiphysis allow to conclude that the daily mean of the rate of excretion of sodium ions decreases in comparison with the animals that were kept under pineal gland (PG) hyperfunction of the filtration fraction and reabsorption of sodium ions are reduced compared to the control animals and rats which were kept under conditions of PG hyperfunction and accompanied by stable indicators of the concentration the specified cation in the blood plasma during the observation period. The action of the blockade NO synthesis in conditions of PG hyperfunction leads to a decrease in the distal transport bridge of sodium ions with a maximum in the day and night intervals of the day the position of the acro- and batiphase of the rhythm changes as compared with the control animals.

THE ROLE OF CYTOKINES IN THE KIDNEY DYSFUNCTION UNDER CONDITIONS OF IRRITABLE BOWELS SYNDROME DEVELOPMENT

The research is dedicated to the elucidation of the cytokines’ role in the renal dysfunction under conditions of irritable bowels syndrome.Objective - to carry out pathological analysis of cytokines’ role of the blood plasma in the kidney dysfunction at irritable bowels syndrome with constipation and diarrhea.Material and methods. 60 patients (18 – men, 42 – women aged 28 to 62 years) with irritable bowels syndrome were examined. Among them there were 28 patients with irritable bowels syndrome with constipation, 32 patients had irritable bowels syndrome with diarrhea. Control group consisted of 25 practically healthy patients. The level of cytokines was determined in the blood plasma: necrosis factor of tumor-alpha, interleukin- 1-beta, interleukin-4 and interleukin-6. Statistical data processing was conducted by means of computer programs “Statgrafics” and “Exel 7.0”.Results. Contents increase of necrosis factor of tumor-alpha, interleukin-1-beta, interleukine-4 and interleukine-6 is accompanied by inhibition of the total, enzymatic, non-enzymatic fibrinolytic activity of the urine and proximal reabsorption of sodium ions in patients with irritable bowel syndrome.Conclusions. More significant imbalance manifestations of cytokines and functional state of kidneys revealed in patients with the syndrome of irritable bowels with diarrhea in comparison with the previously mentioned syndrome with constipation are explained by the development of dehydration, hemoconcentration, hypoxia, lipid peroxidation activation and more essential damageable manifestations of inflammation process due to diarrhea.

Clinical efficiency of desmopressin and cyclooxygenase inhibitor use in incontinent women

Hypothesis/aims of study. Questions regarding the pathogenesis of urine incontinence and methods of treatment are acti vely discussed by gynecologists, urologists, and neuropathologists. Urine incontinence often has multifactor origins: the causes of urine incontinence are connected, as a rule, with the violation of urine continence functional mechanisms, anatomotopographical features of the lower urinary tract, or an premature ovarian failure. Simultaneously, changes in kidney function play a role in the pathogenesis of urine incontinence. In some cases, urine incontinence is combined with urine overproduction or inversion of the circadian rhythm of renal function owing to a decrease in the reabsorption of sodium ions in the thick ascending limb of the loop of Henle. In some patients, we successfully normalized ion transport, diuresis, and circadian rhythm of urine production by desmopressin or diclofenac administration. The present analysis was undertaken to evaluate the clinical efficiency of desmopressin and diclofenac in incontinent patients with nocturnal polyuria and polyuria.
 Study design, materials, and methods. In total, 130 patients with complaints of urinary incontinence, polyuria (24-h urine volume of 40 mL/kg bodyweight or above), or nocturnal polyuria (nocturnal volume/24-h urine volume of 0.33 or above); 30 incontinent women without polyuria or nocturnal polyuria (comparison group); and 14 control subjects were included. The mean patient age was 43.6 ± 4.5 years (41.8 ± 3.7 years in the comparison group and 39.4 ± 6.3 years in the control group, p > 0.05). All the participants performed seven days of urine collection to determine the voided volumes. Patients with polyuria or nocturnal polyuria performed the 3-fold 24-h pad-test. Patients with polyuria and nocturnal polyuria were examined twice: in the initial state and one month after the start of treatment with the optimal dose of diclofenac or desmopressin (Minirin).
 Results. The use of both diclofenac or desmopressin in patients with various types of urine incontinence, polyuria, or nocturia decreased the volume of voided urine because of the normalization of diuresis and an increase in cystometric bladder capacity.

Heat acclimation causes a linear decrease in sweat sodium ion concentration

The purpose of this study was to determine the time course for the previously reported reduction in sweat sodium ion concentration during heat acclimation. Four healthy volunteers completed 7 consecutive days of heat acclimation which included 2h of treadmill walking in a 40°C and 40% relative humidity environment. A modified constant hyperthermia protocol was used as workloads were increased each day to maintain a constant core temperature over the 7 days of heat acclimation. Forearm sweat was collected 3 times during each 2h exercise bout on days 1, 3, 5, and 7 of heat acclimation. Forearm sweat rate and sweat sodium ion concentration were determined from each sample. The results showed that there was a significant (p < 0.05) downward shift in the mean sweat rate vs. sweat sodium ion concentration relationship on days 3, 5, and 7 of heat acclimation, as compared to the pre-heat acclimation (day 1) data. Thus, at any given sweat rate, heat acclimation resulted in a significantly lower sweat sodium ion concentration. The response was very rapid and occurred following only 2 consecutive days of heat exposure (i.e., day 3 vs. day 1 data). Furthermore, the calculated sweat sodium ion concentration, at a sweat rate of 1µl/cm2/min, decreased linearly (r = − 0.50, p < 0.05) during the 7 days of heat acclimation. Such results suggest that heat acclimation rapidly improves sodium ion reabsorption from the eccrine sweat gland duct as evidenced by significant reductions in the sweat sodium ion concentration.

ВПЛИВ ВОДИ ВІД’ЄМНОГО ОКИСНО-ВІДНОВНОГО ПОТЕНЦІАЛУ НА ФУНКЦІЮ НИРОК В ОЛІГУРИЧНІЙ СТАДІЇ СУЛЕМОВОЇ НЕФРОПАТІЇ

Відомо, що зниження окисно-відновного потенціалу води на кожні 59 мВ призводить до збільшення кількості електронів у 10 разів.Мета дослідження – з’ясувати вплив навантаження водою від’ємного окисно-відновного потенціалу на показники функції нирок, порівняно з індукованим діурезом звичайною водогінною водою в олігуричній стадії сулемової нефропатії.Матеріали і методи. У дослідах на 40 білих нелінійних статевозрілих щурах-самцях в олігуричній стадії сулемової нефропатії, яку моделювали за умов гіпонатрієвого раціону харчування шляхом підшкірного введення сулеми в дозі 5мг/кг, при навантаженні водою від’ємного окисно-відновного потенціалу (-232,0±25,12) мВ, порівняно з індукованим діурезом звичайною водогінною водою (окисно-відновний потенціал (88,7±18,35) мВ, який вимірювали ОВП-метром, досліджено екскреторну, іонорегулювальну та кислоторегулювальну функції нирок.Результати досліджень та їх обговорення. За умов досліду встановлено гальмування діурезу та відносного діурезу, що поліпшенням покращанням реабсорбції іонів натрію в проксимальних і дистальних канальцях за рахунок збільшення постачання електронів до канальців нирок. Зазначене положення підтверджено за допомогою багатофакторного регресійного аналізу, оскільки тенденції до наростання дистальної та проксимальної реабсорбції іонів натрію призвели до зменшення синдрому втрати іонів натрію з сечею із тенденцією наростання його концентрації в плазмі крові та встановленням достовірних корелятивних зв’язків (р&lt;0,05) між вищезазначеними показниками. Покращання енергетичного стану проксимального відділу нефрона за умов досліду призвело до поліпшення реабсорбції білка та зменшення його екскреції з сечею. У результаті зазначених змін відбулося зниження постачання іонів натрію до macula densa дистального відділу нефрона, гальмування тубуло-гломерулярного зворотного зв’язку із зниженням реактивності ренін-ангіотензин-альдостеронової системи та зменшенням концентрації і екскреції іонів калію із сечею. Зниження екскреції аміаку зумовлені олужнювальними властивостями мікрогідрину, що викликало гальмування амоніогенезу, який зазвичай активується при некомпенсованих ацидозах.

Involvement of Glucagon-Like Peptide-1 in the Regulation of Selective Excretion of Sodium or Chloride Ions by the Kidneys.

An increase of total glucagon-like peptide-1 (GLP-1) concentration in the plasma in rats was revealed 5 min after oral, but not intraperitoneal administration of NaCl or Trizma HCl solutions. The increase in GLP-1 level was similar to that after oral glucose administration. After intraperitoneal administration of 2.5% NaCl, GLP-1 mimetic exenatide accelerated natriuresis and urinary chloride excretion. Under conditions of normonatriemia and hyperchloremia induced by injection of 6.7% Trizma HCl, exenatide stimulated chloride excretion and reabsorption of sodium ions in the kidneys. These findings suggest that GLP-1 participates in selective regulation of the balance of sodium and chloride ions.

The mechanism of glucagon-like peptide-1 participation in the osmotic homeostasis.

We have found the physiological mechanism of intensification of the excessive fluid removal from the body under the action of glucagon-like peptide-1 and its analog exenatide. Under the water load in rats, exenatide significantly increased the clearance of lithium, reduced fluid reabsorption in the proximal tubule of the nephron and intensified reabsorption of sodium ions in the distal parts, which contributed to the formation of sodium-free water and faster recovery of osmotic homeostasis. Blocking this pathway with a selective antagonist of glucagon-like peptide-1 receptors slowed down the elimination of excessive water from the body.

Functional state of kidneys after injection of fetal liver cells to the rats with water and salt drinking regime under the conditions of acute sublimate nephropathy

The experiments on non linear white rats with acute sublimate nephropathy showed that in 7 days after intraperitoneal injection of fetal liver cells (FLC ) of rats plasma creatinine concentration decreased and proximal reabsorption of sodium ions increased independently of water or salt drinking regime. The increase of natremia in rats that used tap water excluded regulatory influence of FLC on the processes of maintenance of sodium balance under the conditions of experiment. Usage of 0.9 % NaCl solution leads to increase of glomerular filtration rate, activation of tubular transport of sodium ions with predominant elevation of reabsorption in the proximal part of nephron, reduction of sodium ions loss with urination. That points to substantial role of salt drinking regimen in additional beneficial effects of FLC on renal processes in rats with acute sublimate nephropathy.

Effect of Heat Acclimation on Lactate Excretion Rate and Sodium Ion Reabsorption Rate during Exercise

Sweat production requires two Na+/K+-ATPase energy dependent processes: (i) isoosmotic precursor sweat formation in the secretory coil, and (ii) sodium ion reabsorption along the distal sweat duct. Sweat lactate production has been hypothesized to reflect glycolytic ATP-resynthesis for both processes. Research suggests that heat acclimation does not alter sweat lactate concentration ([Lactate]). This is hard to rationalize considering heat acclimation is reported to increase sweat production and sodium ion reabsorption, which are the energy dependent processes. PURPOSE: (1) To determine the relationships during exercise between sweat rate (SR) and sodium ion reabsorption rate (NaRR), and exercise intensity and lactate excretion rate (LER), and (2) to determine whether heat acclimation affects these relationships. METHODS: Six subjects completed an eight-day heat acclimation protocol comprised of 90-minutes treadmill walking in an environmental chamber set at 39°C and 40% relative humidity. Subjects performed three, 30-minute exercise bouts at 30, 40, and 50% of their previously determined VO2max. Sweat rate was measured volumetrically during each bout on the flexor surface of the proximal half of the forearm. [Lactate] was measured and multiplied by forearm SR to calculate LER. Variables of interest were analyzed using non-parametric Friedman tests. RESULTS: LER, and ratios of LER to NaRR, and [Lactate] to SR were not significantly different between the 30, 40, and 50% workloads or between pre and post-heat acclimation based on 95% confidence intervals. Additionally, these relationships were not significantly different between the three workloads on the first or last day of heat acclimation except for LER to NaRR (p<0.05), which increased from 0.05 ± 0.02 to 0.08 ± 0.02 from 30 to 50% of VO2max. CONCLUSION: These data suggest that sweat gland ATPase activity does not increase as a function of exercise intensity, as demonstrated by LER and NaRR remaining relatively constant. Heat acclimation does not appear to affect these relationships.

Vasopressin-dependent coupling between sodium transport and water flow in a mouse cortical collecting duct cell line

Water balance is achieved through the ability of the kidney to control water reabsorption in the connecting tubule and the collecting duct. In a mouse cortical collecting duct cell line (mCCD(c11)), physiological concentrations of arginine vasopressin increased both electrogenic, amiloride-sensitive, epithelial sodium channel (ENaC)-mediated sodium transport measured by the short-circuit current (Isc) method and water flow (Jv apical to basal) measured by gravimetry with similar activation coefficient K(1/2) (6 and 12 pM, respectively). Jv increased linearly according to the osmotic gradient across the monolayer. A small but highly significant Jv was also measured under isoosmotic conditions. To test the coupling between sodium reabsorption and water flow, mCCD(c11) cells were treated for 24 h under isoosmotic condition with either diluent, amiloride, vasopressin or vasopressin and amiloride. Isc, Jv, and net chemical sodium fluxes were measured across the same monolayers. Around 30% of baseline and 50% of vasopressin-induced water flow is coupled to an amiloride-sensitive, ENaC-mediated, electrogenic sodium transport, whereas the remaining flow is coupled to an amiloride-insensitive, nonelectrogenic sodium transport mediated by an unknown electroneutral transporter. The mCCD(c11) cell line is a first example of a mammalian tight epithelium allowing quantitative study of the coupling between sodium and water transport. Our data are consistent with the 'near isoosmotic' fluid transport model.

Exercise reduces airway sodium ion reabsorption in cystic fibrosis but not in exercise asthma

When ventilating large volumes of air during exercise, airway fluid secretion is essential for airway function. Since these are impaired in cystic fibrosis and exercise-induced asthma, it was the aim of this study to determine how exercise affects airway Na(+) and Cl(-) transport and whether changes depend on exercise intensity. Nasal potential was measured in Ringer's solution, with amiloride to block Na(+) transport, and in low chloride-containing isoproterenol to assess Cl(-) channels. Nasal potential was measured at rest and during submaximal and maximal bicycle ergometer exercise in individuals with cystic fibrosis, exercise-induced asthma and controls. At rest, nasal potential was significantly higher in cystic fibroses than in the others. Maximal exercise decreased nasal potentials in cystic fibrosis and controls but not in exercise asthma. Submaximal exercise decreased nasal potentials only in cystic fibrosis. Cl(-) transport was not affected. Our results indicate that nasal potentials and Na(+) transport were decreased by maximal exercise in healthy and cystic fibrosis, whereas submaximal exercise decreased potentials in cystic fibrosis only. Exercise did not affect nasal potentials in asthmatics. Decreased reabsorption during exercise might favour airway fluid secretion during hyperpnoea. This protective effect appears blunted in patients with exercise-induced asthma.

Sodium ion concentration vs. sweat rate relationship in humans

The purpose of this study was to determine the effect of active heat acclimation on the sweat osmolality and sweat sodium ion concentration vs. sweat rate relationship in humans. Eight healthy male volunteers completed 10 days of exercise in the heat. The mean exercising heart rate and core temperature were significantly decreased (P < 0.05) by 18 beats/min and 0.6 degrees C, respectively, following heat acclimation. Furthermore, sweat osmolality and the sweat sodium ion concentration vs. sweat rate relationships were shifted to the right. Specifically, the slopes of the relationships were not affected by heat acclimation. Rather, heat acclimation significantly reduced the y-intercepts of the sweat osmolality and sweat sodium relationships with sweat rate by 28 mosmol/kgH(2)O and 15 mmol/l, respectively. Thus there was a significantly lower sweat sodium ion concentration for a given sweat rate following heat acclimation. These results suggest that heat acclimation increases the sodium ion reabsorption capacity of the human eccrine sweat gland.

Study of Development of Function of Kidneys and Their Regulation on the Background of Pathological Process

By the example of reabsorption of sodium ions in kidney, it is shown that this process, alongside with establishment of the system of osmotic concentration, plays the key role in evolution of renal function. There is shown a similarity of tendencies of changes of the total sodium ion reabsorption in children’s kidney in the process of development and in a series of representatives of various vertebrate classes. An opposite tendency is revealed during the kidney dysfunction produced by chronic renal failure. At all stages of postnatal ontogenesis in healthy children and in adults, kidney maintains the same parameters of the blood serum ion composition and osmolality. A new approach to study evolution of functions is proposed, which is based on a combination of two L.A. Orbeli’s methods—ontogenetic and clinical, by the example of study of renal function and its regulation during development of a pathological process on the background of formation of function in postnatal ontogenesis. When using such approach in children with nocturnal enuresis, significance of autacoids in regulation of urine formation is established. In the case of acute pneumonia in children, a possibility of extrapituitary production of vasopressin-like substances in lungs is shown. In norm, in postnatal ontogenesis of healthy children, in regulation of renal functions and of diuresis system, effects of efferent nerves and hormones (vasopressin) dominate, while significance of autacoids is minimal. But at a dysfunction produced by a pathological process, a change of ratio of activities of these regulatory systems is revealed. The obtained data indicate importance of the clinical and experimental methods proposed by L.A. Orbeli in analysis of evolution of renal functions and study of the nature of regulations. A combination of several methods of evolutionary physiology in one study allows revealing new mechanisms underlying regulation of function and promotes formation of concepts about regularities of evolution of functions.