Hypertonic NaCl Solution Research Articles

Treatment with hypertonic saline versus normal saline nasal wash of pediatric chronic sinusitis

Background: Chronic sinusitis (CS) is a common disease in children, especially those with allergies, that is caused by impaired drainage from the sinuses. Hypertonic NaCl solution has been shown to increase mucociliary clearance and ciliary beat frequency. Objective: We performed a randomized double blind study to compare the effect of nasal wash with hypertonic saline (HS) (3.5%) versus normal saline (NS) (0.9%) on CS. Methods: Thirty patients with CS aged 3 to 16 years were studied. They were randomly divided into two treatment groups matched by age and severity of the disease. Each individual was treated with either HS or NS for 4 weeks. All patients were evaluated by two clinical scores (cough and nasal secretions/postnasal drip [PND]) and by a radiology score at the beginning of the study and after 4 weeks. Results: The HS group improved significantly in all scores (average ± SD): cough score, from 3.6 ± 0.51 to 1.6 ± 0.74; nasal secretion/PND score, from 2.86 ± 0.35 to 1.6 ± 0.74; and radiology score, from 8.06 ± 1.28 to 2.66 ± 1.04. The NS treatment group showed significant improvement only in the PND score (from 2.66 ± 0.49 to 1.53 ± 0.83) but no significant change in both the cough score (from 3.53 ± 0.52 to 3.33 ± 0.49) and the radiology score (from 8.13 ± 1.25 to 7.86 ± 0.91). Clinical observation 1 month after the end of the study showed no change compared with the end of the study in both groups. Conclusion: HS nasal wash is an efficient treatment of CS.(J Allergy Clin Immunol 1998;101:602-5)

Polyamines are required for microtubule formation during gastric mucosal healing.

Polyamines are essential for the repair of gastric and duodenal erosions. Concentrated NaCl (3.4 M) given intragastrically damages the oxyntic gland mucosa and increases the activity of gastric mucosal ornithine decarboxylase (ODC), the first rate-limiting enzyme in polyamine synthesis. The nature of the process of restitution of damaged mucosa is not well known, except that cell migration and the actin cytoskeleton play a prominent role. Microtubules are cytoskeletal components essential for cell migration. The present investigation determines the relationship between polyamines, the distribution of microtubules, and gastric healing in mucosa damaged with hypertonic NaCl solution. Rats were fasted for 22 h and then given 1.0 ml of 3.4 M NaCl intragastrically. Animals were killed 1, 2, 4, 8, and 10 h after 3.4 M NaCl. The oxyntic gland mucosa was removed, and tubulin was visualized by immunofluorescence. Microtubule density was increased around and below the damaged mucosa in the upper one-third of the glandular epithelium at 2 and 4 h and returned to near control levels by 10 h. In rats damaged with 3.4 M NaCl and pretreated intraperitoneally with alpha-difluoromethylornithine (DFMO), a specific inhibitor of ODC, microtubule content was reduced significantly at all time points after NaCl treatment. Addition of spermidine after pretreatment with DFMO and 3.4 M NaCl significantly prevented the effects of DFMO. Colchicine, a potent microtubule-disrupting drug, significantly delayed normal gastric mucosal healing with no effect on ODC activity. These data show that polyamines influence the distribution of microtubules during damage in vivo and indicate a partial mechanism for the dependency of mucosal healing on polyamines.

Schedule-Induced Polydipsic Consumption of Hypertonic NaCl Solutions: Effects of Chlordiazepoxide

LOBARINAS, E. AND J. L. FALK. Schedule-induced polydipsic consumption of hypertonic NaCl solutions: Effects of chlordiazepoxide. PHYSIOL BEHAV 63(3) 419–423, 1998.—Rats were exposed to daily, 3-h sessions of schedule-induced polydipsia (SIP) in which either water, hypertonic NaCl solution (1.5% or 2.2%), or concurrent water and 1.5% NaCl were available. Each condition was in effect for several, consecutive weeks. Presession subcutaneous injections of chlordiazepoxide (CDZP) produced dose-related increases in the polydipsic ingestion of both NaCl solutions but had smaller and less certain effects on water consumption. Under the concurrent-fluid presentation condition, CDZP primarily increased NaCl solution consumption. Conditions generating SIP may function to attenuate what might be viewed as the punishing effects of ingesting highly hypertonic NaCl solutions, thereby permitting the chronic self-administration of large, daily amounts. Like many benzodiazepines, CDZP can attenuate the effects of punishment and thereby also increase NaCl solution ingestion. The two sources of punishment attenuation may be additive, with both differentially effecting greater increases in hypertonic NaCl ingestion, compared to water, when both fluids are presented concurrently.

The gain of the hepatorenal reflex in anesthetized dogs

To determine the overall gain of the hepatorenal reflex, hypertonic NaCl solutions were infused into the portal vein or inferior vena cava of anesthetized dogs at a rate of 0.01 ml/kg/min for 30 min and the urinary Na excretion measured. Infusion of 2.25% NaCl into either the portal vein or inferior vena cava had no effect. Portal infusion of 4.5% or 9% NaCl produced an increase of 36±16 or 40±17 μeq/kg/30 min, respectively, while inferior vena caval infusion had no effect. With 13.5% NaCl infusion, a significant increase in the natriuretic response was seen with portal venous infusion, with no significant difference between portal venous and inferior vena caval infusion. Thus, the difference in the natriuretic response between portal venous and inferior vena caval infusion was dependent on the degree of input; when an appropriate input was given, natriuresis was induced only by portal venous infusion, probably mediated by the hepatorenal reflex. The gain of the hepatorenal reflex was calculated from the output divided by the input. When 4.5% or 9% NaCl was infused into the portal vein, the 2-h gain of the hepatorenal reflex was 0.38±0.15 or 0.34±0.14, respectively.

Osmotically Induced Conductance and Capacitance Changes in in vitro Perfused Rectal Gland Tubules of Squalus acanthias

The rectal gland of Squalus acanthias is critically involved in the homeostasis of NaCl and water metabolism and hence in overall osmoregulation. In the present study, we have examined the acute responses of rectal gland slices and in vitro perfused rectal gland tubule (RGT) cells to the exposure to dilute and hypertonic peritubule solutions. Five series were performed. (i) With changes in osmolality, Western blots to monitor tyrosine, threonine and serine phosphorylation in rectal gland slices did not reveal clear–cut changes in phosphorylation patterns. All other series were performed in in vitro perfused RGT. (ii) Relative cell volume was estimated by fura–2 fluorescence using the emission at the isosbestic excitation wavelength of 360 nm. Hypotonic solution (–100 mmol/l NaCl) reduced fura–2 fluorescence by 16% and hypertonic solution (+100 mmol/l NaCl) had the opposite effect (+12%). (iii) Transepithelial resistance was increased markedly by hypotonic solution, probably by cell swelling, and the opposite was seen with hypertonic solutions. (iv) Whole–cell patch clamp experiments indicated that hypotonic solution hyperpolarized the cells, and increased membrane conductance and membrane capacitance. The latter two changes correlated significantly with each other. Hypertonic solution had the opposite effect. (v) Measurements of the fura–2 fluorescence ratio (340/380 nm) revealed that hypotonic solution (–NaCl) increased cytosolic Ca²⁺ activtiy ([Ca²⁺]_i). Hypertonic solution had no detectable effect on [Ca²⁺]_i. These data indicate that RGT cells are swollen by removal of NaCl from the bath solution. This causes an increase in [Ca²⁺]_i and a predominant increase in K⁺ conductance and hyperpolarization. Urea apparently permeates these cells quite well and its addition (+U) or its removal (–U) had only moderate osmotic effects. The removal of urea and replacement by mannitol produced effects similar to those seen with hypertonic NaCl solution.

Acute osmotic/stress stimuli induce a transient decrease of transcriptional activity in the neurosecretory neurons of supraoptic nuclei.

Administration of hypertonic NaCl solutions by intraperitoneal injection evokes a transient expression of immediate-early genes in the hypothalamic magnocellular neurons of supraoptic nuclei (SON), which is followed by an upregulation of arginine vasopressin synthesis and a general increase in cellular metabolic activity. Here we have analysed the changes that occur in the nucleus of SON neurons during the period of transient Fos expression after injection of hypertonic saline. Within the first 30 minutes after injection, the nuclei become significantly smaller, contain more condensed chromatin and incorporate less 3H-uridine than the controls. By 12 hours these effects are reverting and at 24 hours the nuclei are already more active than the controls. Additionally, we observe an initial decrease in the number of coiled bodies per nucleus within the first 2 hours, followed by a 3-fold increase at 24 hours after injection. As coiled bodies are transcription-dependent subnuclear 'organelles', these results further support the view that injection of hypertonic saline causes a transient inhibition of nuclear activity. Our data show that SON neurons respond to acute osmotic/stress stimuli first with inhibition and then with activation of gene expression. Importantly, inhibition of transcriptional activity occurs simultaneously with maximal accumulation of Fos protein in the nucleus, raising the possibility that activation of c-fos expression may cause repression of target genes.

Effects of antihypertensive treatment on vasopressin secretion and on its osmoregulation in moderate hypertension.

Changes in plasma osmolality and arterial pressure can affect the secretion of vasopressin (AVP). To investigate the effect of a drug-induced lowering of the arterial pressure on the plasma concentration of AVP and on its osmoregulation in moderately severe uncomplicated hypertensives. A group of 33 moderate uncomplicated and untreated essential hypertensives of both sexes (mean age 48 +/- 1 years, average arterial pressure 171 +/- 3/108 +/- 2 mmHg) was studied. We measured AVP and other plasma and urine variables in 21 of them before and after administration of a hypertonic NaCl solution (100 mmol NaCl in 50 ml). Antihypertensive treatment with a single drug or, if necessary, with a combination of drugs was initiated for eight of these subjects and hypertonic saline administration was repeated after 1 month of treatment. The hypertonic stimulus was administered to the other 12 subjects after acute lowering of the arterial pressure by continuous intravenous infusion either of 0.3 mg clonidine in 100 ml (n = 6) or of 50 mg sodium nitroprusside in 250 ml (n = 6). Administration of hypertonic saline to untreated hypertensives increased their AVP level from 1.6 +/- 0.28 to 5.4 +/- 0.7 pg/ml (n = 21, P < 0.01). Their mean arterial pressure was lowered after pharmacological treatment for 1 month (n = 8) from 125 +/- 2 to 101 +/- 2 mmHg; their baseline AVP level remained unchanged (1.2 +/- 0.21 versus 0.9 +/- 0.25 pg/ml); after hypertonic saline had been administered to hypertensives with lowered arterial pressures, their AVP level increased to 6.0 +/- 1.03 pg/ml (P < 0.01). The AVP level in subjects whose MAP had been lowered acutely by administration of clonidine (n = 6) or of sodium nitroprusside (n = 6; on the average, from 132 +/- 3 to 110 +/- 4 mmHg) increased concurrently from 1.6 +/- 0.63 to 3.4 +/- 0.7 pg/ml (P < 0.05); after administration of the hypertonic saline the AVP level increased to 10.8 +/- 2.22 pg/ml (P < 0.01). This stimulated value was significantly (P < 0.01) higher than that observed after hypertonic saline had been administered to untreated hypertensives (5.4 +/- 0.7 pg/ml). Acute lowering of the arterial pressure in moderate essential hypertension appears to facilitate the secretion and osmoregulation of AVP. On the other hand, during prolonged antihypertensive treatment, baroreflex regulation of the secretion of AVP appears to be set at a lower operating point, thus exerting the same influence on the release of AVP as it did before antihypertensive treatment.

Potassium depletion modulates aldose reductase mRNA in rat renal inner medulla

The organic osmolytes present in renal inner medullary cells balance the extracellular hyperosmolality and protect the cell against the effects of high salts and urea. We previously demonstrated that a renal concentrating defect due to potassium depletion was associated with a decrease in organic osmolytes including sorbitol. However, we could not determine whether a reduction in medullary organic osmolyte would be cause or effect of urine concentration defect associated with potassium depletion. We focused on the synthesis of sorbitol catalyzed by the enzyme, aldose reductase. To clarify whether the treatment of potassium depletion would affect aldose reductase when extracellular tonicity, and medullary sodium or potassium was maintained at the level of control rats, we administered a hypertonic solution of NaCl or KCl to potassium-depleted rats and evaluated aldose reductase enzymatic activity and mRNA abundance as well as the medullary contents of organic osmolytes. Either infusion significantly reduced tissue sodium content in potassium-depleted rats. With KCl infusion protocol but not that of NaCl, sorbitol as well as aldose reductase mRNA abundance increased to the control level. Medullary contents of other organic osmolytes exhibited a pattern similar to sorbitol. Data suggested that aldose reductase mRNA abundance was reduced in potassium depletion irrespective of medullary sodium content. A decrease in sorbitol level may precede a urinary concentrating defect. Our finding constitutes the first demonstration of the relationship between a potassium deficiency and the abundance of aldose reductase mRNA, an osmoregulatory protein in the kidney.

Angiotensin II-induced thirst, but not sodium appetite, via AT1 receptors in organum cavum prelamina terminalis.

The angiotensin receptor specificity, with respect to fluid intake, of the organum cavum prelamina terminalis (OCPLT), a recently discovered discrete forebrain structure with high sensitivity to angiotensin II (ANG II), was investigated. ANG II (10 ng) microinjected into the OCPLT significantly increased water consumption but did not induce intake of a hypertonic (3%) NaCl solution. Losartan, an ANG II type 1 (AT1) receptor-specific antagonist, produced dose-related (1-100 ng) inhibition of ANG II-induced drinking. The ANG II type 2 receptor-specific antagonist CGP-42112A was ineffective. Intake of the 3% NaCl solution in response to microinjection of either of the antagonists into the OCPLT was never observed. These findings suggest that water intake produced by microinjection of ANG II into the OCPLT is mediated by AT1 receptors uniquely and that, in contrast to other regions of the brain, these receptors do not induce salt intake when stimulated by ANG II.

Induction of sperimidine/spermine N1-acetyltransferase in rat gastric mucosa by administration of hypertonic NaCl solution

Induction of sperimidine/spermine N1-acetyltransferase in rat gastric mucosa by administration of hypertonic NaCl solution

Effects of ethanol, caffeine, and clorazepate on hypertonic NaCl solution intake in rats

Previous reports indicate that several anxiolytics enhance the intake of hypertonic saline in rehydrating rats. This experiment was conducted to determine the effects of repeated (5 sessions) injection (i.p.) of ethanol (0.4 or 0.8 g/kg), caffeine (20 or 40 mg/kg) or clorazepate (3 mg/kg) on the ingestion of hypertonic saline (1.8%) in water-deprived rats. Saline intake increased with the acute administration of both clorazepate and ethanol (two doses), but it decreased with caffeine (two doses). It seems that the increase or decrease of hypertonic saline ingestion following acute drug administration continues to correlate well with anxiolytic or anxiogenic actions. However, following repeated administration of caffeine and ethanol, the effects on saline intake were not maintained in a reliable manner.

Expression of c- fos immunoreactivity in the hypothalamic magnocellular neurons during chronic osmotic stimulations

The immunoreactivity of c- fos protein was transiently detected in magnocellular neurons of the supraoptic nucleus (SON) and paraventricular nucleus (PVN) of the rat hypothalamus after intraperitoneal injection of hypertonic NaCl solution. In contrast, c- fos-positive magnocellular neurons were persistently observed in the SON and PVN of the rats which were chronically stimulated by the drinking of hypertonic NaCl solution instead of water or by water deprivation. c- fos immunoreactivity was eliminated in the animals which were allowed to drink tap water for 24 h following the chronic osmotic stimulations. These results suggest that persistent expression of c- fos protein is closely associated with the neural plasticity of the hypothalamic magnocellular neuron.

Effect of hypertonic NaCl–starch–solution on oedema of different pathogenesis

Small volumes of hypertonic NaCl-solutions have been proven to restore haemodynamics in hypovolemic shock patients. Topic of this study was to investigate whether bolus application of 7.5% NaCl-6.5% starch-solution (HSS) apart from its relevance in shock might be an effective therapy in oedema. Considering differential therapeutic aspects, the volume effects of 7.2 ml HSS were tested in three types of oedema: hydrostatic oedema induced by venous congestion (n = 6), oedema caused by bradykinin injection (n = 6), and proteinase-induced oedema (n = 6). The arterial, venous pressure and weight changes indicating volume shifts between intra- and extravascular space were continuously monitored in 36 isolated perfused rabbit hindlimbs. Oedema formation was induced corresponding to a weight gain of 18-20 g. Subsequently 7.2 ml HSS were injected into the extracorporeal circulation system containing 200 ml cell free, isoosmotic perfusate. Six experiments of each oedema group without HSS-application served as controls. 75-100% of oedema formation could be remobilised via bolus application of HSS within 5 min in all types of oedema. A persisting weight reduction was detectable in the hydrostatic and bradykinin oedema, whereas in the elastase oedema the initial weight loss was followed by a regain of weight up to 180% of initial oedema formation at 120 min after HSS-application. The results show that, due to the osmotic gradient induced by bolus application of HSS, the hydrostatic and bradykinin oedema can be permanently remobilised, whereas the therapeutic effect during proteinase oedema is only short-lasting due to an irreversible damage of barrier function.

Firing activity of preoptic and supraoptic neurons upon mild alterations in osmo- and glucohomeostasis

Responses of neurons of the lateral (LPO) and medial (MPO) subdivisions of the preoptic region (RPO) and of the supraoptic nucleus (SO) of the hypothalamus at infusions of up to 400 µl of a hypotonic (0.2%) or a hypertonic (0.3%) NaCl solution or an isotonic (5.5%) glucose solution into the homolateral internal carotid artery were studied in acute experiments on ketamine-anesthetized cats. Changes in the firing frequency were exhibited by 69% of the examinedRPO andSO neurons, the response being of four different types: a monophasic increase (1st-type) or a monophasic decrease (2nd-type) in the activity; biphasic responses where an initial frequency rise was followed by inhibition (3rd-type) and vice versa (4th-type). Of all the neuronal responses to all stimulations, 50% (121/245) were of the 1st type; 11% (26/245), of the 2nd type; 5% (14/245), of the 3rd type; and 3% (7/245), of the 4th type. No neurons with 1st-type responses to infusion of the hypotonic NaCl solution were found in the medial sections of theMPO, and of the hypertonic solution, in the lateral sections of theLPO. Neurons with 2nd-type responses to infusion of hypo- and hypertonic NaCl solutions were almost solely detected in theSO, whereas units with such responses to glucose infusions were observed only in theRPO, being fully absent in theSO, where this stimulation gave rise only to 1st-type responses. Neurons with 3rd- and 4th-type responses to hypo- and hyperosmotic stimulations were detected predominantly in theMPO andSO, and to glucose stimulation, in theMPO andLPO.

Studies on the Mechanism of Salt Tolerance in Salicornia europaea L.II. High osmosis of epidermal cells in stem.

To understand how cells sense and respond to salt stress, we investigate changes in plasmolitic concentration to NaCl of epidermal cells in Salicornia europaea during the growth period. The inorganic ion concentration in tissues and plasmolitic responses to NaCl of epidermal cells in wild Salicornia were compared with other halophytes. Cell responses to high salt concentration were compared with plants grown in MS medium as a low salinity. The incipient plasmolytic NaCl concentration in epidermal cells in Salicornia stems rose from 1.6% to 2.2% during the growth period. Main inorganic ions in Salicornia at the end of growth stage were 63 mM Na+ and 107 mM Cl- per 100 g fresh weight. When plants were grown in MS medium, the size of epidermal cells was about 2 fold large, and osmotic pressure in plants was 35-50% low compared with wild plant cells. Incipient plasmolytic NaCl concentration in epidermal cells of plants grown in wild and MS medium was almost same. However, most of the epidermal cells grown in MS medium showed severe plasmolysis under hypertonic NaCl solutions. The results suggest that the cells of Salicornia can accumulate NaCl during the growth period and accumulated NaCl may make adjustment of osmotic pressure in the cells. By contrast with other halophytes, Salircornia showed high Na+ and Cl- concentrations in tissues and high plasmolitic concentration to NaCl in epidermal cells.

Amiloride sensitivity in the neonatal rat.

Amiloride-sensitive sodium channels in taste buds appear to play a key role in the response to NaCl stimulation, at least in adult rats. The researchers examined whether neonatal rats, which display an exaggerated preference for hypertonic NaCl solutions, lack functional amiloride-sensitive sodium channels. NaCl intake was significantly reduced by amiloride pretreatment, but water and ammonium chloride, NH4Cl, were unaffected. The researchers assessed whether the early appearance of amiloride sensitivity was mediated by effects on chorda tympani (CT) activity by sectioning the CT before testing. CT transection reduced intake of NaCl solutions and eliminated evidence of amiloride sensitivity. Amiloride sensitivity was also assessed by recording of whole-nerve CT activity at 8-11 days of age; the response to NaCl stimulation was significantly suppressed by amiloride. These data indicate that amiloride-sensitive sodium channels develop earlier than previously believed.

Salt consumption and body fluid balance during cold exposure in rats

We investigated the effect of exposure to cold on salt consumption and the role of salt consumption on the maintenance of body fluid balance in male Wistar rats. The rats were provided with both tap water and NaCl solution ad lib during 16-h exposure to cold (10°C) and normal (25°C) air temperature conditions. The concentration of the NaCl solution was 0.9% for one group (0.9% NaCl group; n = 7) and 1.8% for the other (1.8% NaCl group; n = 6). At 10°C, weight loss was greater than that at 25°C, and fluid and Na balance were negative in the 0.9% NaCl group. However, the calculated Na concentration of the fluid consumed in the 0.9% NaCl group was about 135 mEq/l Na (0.8% NaCl) at both 10°C and 25°C. In the 1.8% NaCl group, the values indicating fluid and Na balance under both temperature conditions were similar, while the calculated concentration of Na in fluid consumed at 10°C (187 mEq/l Na: 1.1% NaCl) was higher than that at 25°C (153 mEq/l Na: 0.9% NaCl). These results suggest that the consumption of hypertonic NaCl solution indicating increased salt appetite during exposure to cold counteracts the loss of body fluid and Na via urine.

C-fos expression in arcuate nucleus following intracerebroventricular hypertonic saline injections

Experiments were done in conscious rats to investigate the effect of i.c.v. infusions of hypertonic NaCl solutions on the induction of the protein Fos in the arcuate nucleus (Arc). Neurons containing Fos-like immunoreactivity were observed throughout the rostrocaudal extent of Arc after i.c.v. infusions of hypertonic saline solutions (337–744 mM). However, most of the labelled neurons were confined to the middle third of the nucleus, in the region of the dorsomedial and ventromedial subnuclei. Few, if any Fos-labelled neurons were observed in Arc of animals that received i.c.v. infusions of isotonic (142 mM) or mild hypertonic (173 mM) saline solutions or a hyperosmotic (660 mOsm/kg) saline solution of mannitol. No Fos-labelled neurons were found in the subfornical organ, although a few were observed scattered throughout the organum vasculosum laminae terminalis (OVLT) in all the animals studied. The density nor the distribution pattern of Fos-labelled neurons in OVLT was altered in animals receiving i.c.v. infusions of hypertonic saline or hyperosmotic solutions. These data demonstrate that Arc neurons are activated during a hypertonic saline challenge and suggest that Arc may function as a sodium-sensitive structure that is involved in body-fluid and circulatory homeostasis.

Osmotic barrier properties of the rat peritoneal membrane.

In this study the osmotic barrier characteristics of the rat peritoneal membrane were investigated. Fluid movements between the peritoneal cavity and the blood were measured following instillation of isotonic saline (control) and hypertonic solutions of NaCl, glucose, sucrose, raffinose and myoglobin (test solutions). Moreover, 5 and 8% albumin in NaCl were investigated. Osmotic transients were assessed using a simple volume recovery technique. Peritoneal osmotic conductances (i.e. products of peritoneal hydraulic conductances [LpS] and solute reflection coefficients [sigma]) were calculated from the differences in the rates of peritoneal fluid loss and in osmotic pressures between test solutions and the isotonic saline control solution. The osmotic conductance to glucose was estimated to be 1.63 microliters min-1 mmHg-1 m-2 and that for albumin to be 59.6 microliters min-1 mmHg-1 m-2. Assuming an albumin sigma of 0.9, the sigma of glucose was estimated to be 0.025, in accordance with previous measurements for the cat peritoneal membrane. The osmotic conductances assessed here were compatible with an 'overall' peritoneal equivalent small pore radius of 47-48 A, but could also be fitted to a three-pore model of peritoneal permselectivity, including a transcellular (ultra-small pore) pathway and a large pore pathway. The great discrepancy between peritoneal sigma for small solutes and that for albumin obtained in this study indicates that small solute reflection coefficients are close to zero while that for albumin is not far from unity. Furthermore, the peritoneal hydraulic conductance (ultrafiltration coefficient) is large enough to allow for a substantial absorption of fluid directly into the plasma when the crystalloid osmotic pressures in blood and peritoneal dialysate are in equilibrium.

Hyperosmotic Stress Induces Immediate-Early Gene Expression in Ventricular Adult Cardiomyocytes

Mammalian cells possessing osmosensors have long been described in brain and kidney. The genetic basis of the response to hyperosmotic stress has been well characterized in prokaryotes. In contrast, the genetic response of eukaryotic cells is poorly understood. Therefore we investigated the effect of hypertonic NaCl and sucrose solutions on the transcriptional activation of the immediate-early genes (IEGs) egr-1 and c-fos in isolated ventricular adult rat cardiomyocytes. We observed that even small increases in osmolarity to 315 ± 5 mosmol/l and 370 ± 8 mosmol/l by hypertonic NaCl solution resulted in dose-dependent induction of egr-1 (4- and 5-fold) and c-fos (3- and 4-fold), respectively. Hypertonic sucrose solution had the same effect on egr-1 and c-fos mRNA levels while increased sucrose concentration under isotonic conditions had no effect. Cardiomyocytes exposed to hypertonic media did not significantly shrink as shown by a cell length measurement. We conclude that isolated adult cardiomyocytes possess an osmoreceptor mechanism which is able to sense even slight changes in osmolarity and to translate these into a transcriptional response of the myocardial IEG program.