Sodium-deficient Rats Research Articles

Long-Term Sodium Deficiency Reduces Sodium Excretion but Impairs Renal Function and Increases Stone Formation in Hyperoxaluric Calcium Oxalate Rats.

Excessive sodium intake is associated with nephrolithiasis, but the impact of sodium-deficient (SD) diets is unknown. Hence, we investigated the effects of short- and long-term SD diets on the expression of renal aquaporins and sodium transporters, and thus calcium oxalate (CaOx) crystal formation in hyperoxaluria rats. In a short-term sodium balance study, six male rats received drinking water and six received 0.75% ethylene glycol (EG) to induce hyperoxaluria. After a 30-day period of feeding on normal chow, both groups were treated with a normal-sodium diet for 5 days, followed by a sodium-free diet for the next 5 days. In a long-term SD study (42 days), four groups, induced with EG or not, were treated with normal-sodium water and sodium-free drinking water, alternately. Short-term sodium restriction in EG rats reversed the daily positive sodium balance, but progressively caused a negative cumulative water balance. In the long-term study, the abundant levels of of Na/H exchanger, thiazide-sensitive Na-Cl cotransporter, Na-K-ATPase, and aquaporins-1 from SD + EG rats were markedly reduced, corresponding to a decrease in Uosm, as compared to SD rats. Increased urine calcium, AP(CaOx)index, and renal CaOx deposition were also noted in SD + EG rats. Although the SD treatment reduced sodium excretion, it also increased urinary calcium and impaired renal function, ultimately causing the formation of more CaOx crystals.

Effects of CeA lesions on the initiation and expression of sodium appetite in sodium-deficient rats

To investigate the effects of central nucleus of amygdala (CeA) lesion on the initiation and expression of sodium appetite in sodium-deficient rats. Three groups of SD rats (n=6 in each group) were treated with bilateral CeA lesion, sham lesion or no lesion. After the recovery, the rats were fed with low-sodium diets for 14 days to establish a sodium-deficient rat model. The double-bottle selection in single cage test was used to observe the intake of 0.3 mol/L NaCl and DW in 5 timepoint with 24 hours in sodium-deficient rats. Immunofluorescence staining of aldosterone-sensitive neurons in the nucleus tractus solitarii (NTS)was used to investigate the effect of CeA lesion or not on the activity of aldosterone-sensitive neurons in rats with or without sodium deficiency. After fed with low-sodium diet for14 days, the volume and preference rate of 0.3 mol/L NaCl intake of the rats within 24 h were significantly increased compared with those before low-sodium diet (P＜0.01). The intake volume and the preference rate of 0.3 mol/L NaCl in CeA lesion rats were significantly decreased than those in CeA sham lesion rats and normal rats in the sodium-deficient condition (P＜0.01). The CeA lesion had no effects on the activity of aldosterone-sensitive neurons in NTS in rats with low-sodium diet. Low-sodium diet induces an increase in the expression of sodium appetite in rats. CeA lesions inhibit the behavioral expression of sodium appetite in sodium-deficient rats but have no effects on the initiation of sodium appetite in rats with sodium-deficient rats.

Neutrophil responses to injury or inflammation impair peripheral gustatory function

The adult peripheral taste system is capable of extensive functional plasticity after injury. Sectioning the chorda tympani (CT), a primary sensory afferent nerve, elicits transient changes in the uninjured, contralateral population of taste receptor cells. Remarkably, the deficits are specific to the sodium transduction pathway. Normal function is quickly restored in the intact nerve, in parallel with an influx of macrophages to both the denervated and uninjured sides of the tongue. However, changing the dietary environment by restricting sodium blocks the macrophage response and prolongs functional alterations. Since the functional deficits occur before macrophages are present in the peripheral taste system, we hypothesized that neutrophils play a role in modulating neural responses in the intact CT. First, the dynamics of the neutrophil response to nerve injury were analyzed in control-fed and sodium-deficient rats. Nerve sectioning briefly increased the number of neutrophils on both the denervated and uninjured sides of the tongue. The low-sodium diet amplified and extended the bilateral neutrophil response to injury, in parallel with the persistent changes in sodium taste function. To test the impact of neutrophils on taste function, we depleted these cells prior to nerve sectioning and recorded neural responses from the intact CT. This treatment restored normal sodium responses in the uninjured nerve. Moreover, recruiting neutrophils to the tongue induced deficits in sodium taste function in both CT nerves. Neutrophils play a critical role in ongoing inflammatory responses in the oral cavity, and may induce changes in taste perception. We also suggest that balanced neutrophil and macrophage responses enable normal neural responses after neural injury.

Brain vasopressin involvement in behavioral sensitization to amphetamines and drinking hypertonic salt solutions.

Sodium restriction cross-sensitizes rats to the psychomotor effects of amphetamines and activation of brain vasopressin pathways induce a psychomotor sensitization and facilitate salt intake in sodium-deficient rats. In Experiment 1, we tested the hypothesis that male rats previously sensitized to central VP injections would subsequently show enhanced psychomotor responses to amphetamine. Rats were administered either saline, intraventricular injections of VP (50 ng) or amphetamine (1 or 3 mg/kg, d-amphetamine sulfate, i.p.) on two consecutive days. All rats were administered amphetamine on day 3 and behavior was monitored. Amphetamine on day 3 elicited a significantly greater psychomotor response in rats that had two prior injections of amphetamine or VP, than in rats previously treated with saline or those receiving amphetamine for the first time on Day 3. In Experiment 2, the hypothesis that prior experience with central VP would cross-sensitize the rat to drinking hypertonic sodium (NaCl) solutions was tested. Naïve male rats were administered intraventricular injections of VP (50 ng) or isotonic saline for 3 days and on the fourth day non deprived rats were given access to 0.3 M NaCl and water for 1 h. Control (isotonic saline treated) rats only drank 1 ml of 0.3 M NaCl, but need-free rats previously exposed to central VP injections drank significantly more hypertonic saline (4 ml). These results show that prior experience with central VP cross-sensitizes rats to the psychomotor stimulant effects of amphetamine and the ingestion of concentrated NaCl solutions. Supported by NIH DK50586 and RR15640.

Intraventricular injections of tachykinin NK3 receptor agonists suppress the intake of “salty” tastes by sodium deficient rats

Intraventricular injections of the tachykinin NK3 receptor (NK3-R) agonist, senktide, suppress the ingestion of hypertonic (0.5 M) NaCl by decreasing the initial lick rate and accelerating the decay in lick rate in sodium deficient rats. The present experiment examined whether the effects of intraventricular injections of senktide on lick rate were selective for NaCl solution, or if the ability of NK3-R agonists to inhibit intake generalizes other sodium-containing solutions. The effects of lateral ventricular injections of isotonic saline or senktide (200 ng) on intake and lick rate of 0.5 M solutions of sodium chloride (NaCl), sodium acetate (Na acetate), sodium bicarbonate (Na bicarbonate), and monosodium glutamate (MSG) were measured in sodium deficient rats. Compared to saline injection, senktide injection had no effect on the lick rate or intake of Na bicarbonate. In contrast, intraventricular injection of senktide suppressed the intake of NaCl, Na acetate, and MSG compared to saline injection. Senktide injection accelerated the decay in lick rate for NaCl, Na acetate and MSG, but only suppressed the initial lick rate for NaCl and Na acetate. The results show that activation of NK3-R in sodium deficient rats suppresses the intake of tastes that are classified as “salty” tasting and that the decrease in intake reflects effects on the initial lick rate, the decay in lick rate, or both.

Lipopolysaccharide-induced up-regulation of activated macrophages in the degenerating taste system

Unilateral chorda tympani (CT) nerve section and maintenance on a sodium-restricted diet leads to a rapid decrease in neurophysiological taste responses to sodium in the contralateral, intact CT nerve. Up-regulation of immune function with lipopolysaccharide (LPS; 100 microg i.p.) induces a recovery of normal sodium taste responses, suggesting that the sodium-deficient diet is immunosuppressive. In fact, there is a bilateral increase in the number of lingual, activated macrophages in control-fed rats receiving CT nerve section that does not occur in sodium-deficient rats after sectioning. In the current study, we hypothesized that the LPS-induced recovery of normal taste function in sodium-deficient rats is based on an increase in the activated macrophage response to denervation. Rats receiving a unilateral CT nerve section, a sodium-restricted diet, and/or an injection of LPS (100 microg; i.p.) were overdosed with pentobarbital at day 2 postsectioning, and tongues were rapidly dissected and frozen. Cryosections were then immunohistochemically stained to determine the percentage of ED1 staining for activated macrophages or the number of alphabeta or gammadelta T cells. Activated macrophage levels were significantly increased in sodium-restricted rats that received LPS following unilateral CT nerve section, supporting our hypothesis. These novel findings suggest that LPS overcomes the immunosuppression induced by the sodium-restricted diet and also indicate that the immune system plays a role in regulating taste function after neural injury.

Body sodium and volume homeostasis.

maintenance of a “milieu interieur,” which allows our cells to function away from the ancient sea, is one of the most important functions of the body. Maintenance of constant extracellular osmolarity and sodium concentration depends on a precise balance between intake and excretion of sodium and

Brain vasopressin and sodium appetite.

Intraventricular injections of vasopressin (VP) and antagonists with varying degrees of specificity for the VP receptors were used to identify the action of endogenous brain VP on 0.3 M NaCl intake by sodium-deficient rats. Lateral ventricular injections of 100 ng and 1 microg VP caused barrel rotations and a dramatic decrease in NaCl intake by sodium-deficient rats and suppressed sucrose intake. Intraventricular injection of the V(1)/V(2) receptor antagonist [d(CH(2))(5)(1),O-Et-Tyr(2),Val(4), Arg(8)]VP and the V(1) receptor antagonist [d(CH(2))(5)(1),O-Me-Tyr(2),Arg(8)]VP (MeT-AVP) significantly suppressed NaCl intake by sodium-deficient rats without causing motor disturbances. MeT-AVP had no effect on sucrose intake (0.1 M). In contrast, the selective V(2) receptor antagonist had no significant effect on NaCl intake. Last, injections of 100 ng MeT-AVP decreased mean arterial blood pressure (MAP), whereas 100 ng VP elevated MAP and pretreatment with MeT-AVP blocked the pressor effect of VP. These results indicate that the effects produced by 100 ng MeT-AVP represent receptor antagonistic activity. These findings suggest that the effect of exogenous VP on salt intake is secondary to motor disruptions and that endogenous brain VP neurotransmission acting at V(1) receptors plays a role in the arousal of salt appetite.

Differential effects of intraventricular injections of tachychinin NK-sub-1 and NK-sub-3 receptor agonists on normal and sham drinking of NaCl by sodium-deficient rats.

The effects of lateral ventricular injections of succinyl-[Asp6, N-Me-Phe8]-substance P (SENK; 25, 100, 200 ng), a tachykinin NK3 receptor agonist, and [Sar9, Met(O2)11]-substance P (Sar Met; 100, 200 ng), an NK1 receptor agonist, on normal (gastric fistula closed) and sham drinking (gastric fistula open) of hypertonic NaCl by sodium-deficient rats were compared. Intraventricular injections of Sar Met had no effect on NaCl intake in either condition. Injections of 100 ng and 200 ng SENK caused an equal suppression of NaCl intake in the 2 fistula conditions. The latency to drink was not affected, but the initial lick rate was significantly lower and decayed more rapidly after 100 ng SENK than after saline or 25 ng SENK. The results show that (a) the tachykinin subtypes are not equally involved in the control of need-induced salt intake; (b) negative feedback from the stomach and distal gastrointestinal tract is not required for intraventricular injections of SENK to suppress sodium appetite; (c) the activation of NK3 receptors decreases the oral excitatory influence of hypertonic NaCl in sodium-deficient rats.

Differential effects of intraventricular injections of tachychinin NK₁ and NK₃ receptor agonists on normal and sham drinking of NaCl by sodium-deficient rats.

Differential effects of intraventricular injections of tachychinin NK₁ and NK₃ receptor agonists on normal and sham drinking of NaCl by sodium-deficient rats.

Lateral Ventricular Injections of the NK 3 Agonist Senktide Affect Salt Taste-Elicited Responses

Flynn, F. W. and M. E. Smith. Lateral ventricular injections of the NK 3 agonist senktide affect salt taste-elicited responses. Peptides 19(2) 319–324, 1998.—Central injections of the selective tachykinin NK 3 receptor agonist senktide (SENK) suppresses salt appetite. Also, following SENK, intraoral infusions of hypertonic NaCl elicit fewer ingestive taste reactivity responses and more aversive responses than following intraventricular injections of isotonic saline. This pattern of taste reactivity results suggest that SENK affects the oral stimulating properties of salt taste. Before accepting this interpretation, however, alternative explanations need to be examined. The following experiments evaluated whether the effects of intraventricular SENK injection on taste reactivity could be due to: 1) a general oral motor impairment that reduces ingestive responding to tastes (Experiment 1) or; 2) SENK having aversive consequences (Experiment 2). In Experiment 1, the effects of intraventricular injections of SENK (200 ng) on taste reactivity responses to 0.5 M NaCl and 0.1 M sucrose were measured in sodium deficient rats. Intraoral infusions of 0.5 M NaCl elicited fewer ingestive taste reactivity responses following SENK than injections of isotonic saline in sodium deficient rats. Sucrose continued to elicit the same high number of ingestive taste reactivity responses following intraventricular injections of isotonic saline and SENK. Thus, SENK did not cause a general decrease in ingestive responding. A conditioned taste aversion test was employed in Experiment 2 to determine if SENK had aversive consequences. Rats were given 30 min access to alanine (0.3 M) and were then administered either lithium chloride (LiCl) or intraventricular injections of SENK (200 ng) on three consecutive days. Rats avoided alanine that was paired with LiCl, but those rats that had alanine paired with SENK showed no avoidance of the taste even after three pairings. These results replicate findings that intraventricular injections of the NK 3 agonist SENK decreases the palatability of NaCl (as measured by taste reactivity) and suggest that its effect on NaCl-elicited taste reactivity is not due to the treatment causing a motor impairment or malaise.

Mammalian Bombesin-Like Peptides Suppress Sham Drinking of Salt by Sodium-Deficient Rats

Bombesin (BN) and its mammalian relatives, gastrin-releasing peptide (GRP) and neuromedin B (NMB), have been implicated in the control of food intake, and more recently systemic injections of BN have been shown to suppress need-free and sodium deficiency-induced salt (NaCl) intake. Postoral mechanisms that are activated by the ingestion of salt contribute to the termination of salt intake. The hypothesis that BN-like peptides potentiate postoral salt ingestion-contingent feedback and thereby accelerate the termination of salt intake was evaluated by measuring the effects of peripheral injections of BN (4, 6, 16 μg/kg), GRP (4, 8, 16 μg/kg), and NMB (4, 8, 16 μg/kg) on sham (gastric fistula open) and normal (gastric fistula closed) drinking of NaCl (0.5 M ) by sodium-deficient male rats. Sodium deficiency was induced by injections of deoxycorticosterone acetate and furosemide. Injections of 4 μg/kg BN produced a transient suppression in the sham drinking of salt and a more sustained reduction of salt intake when postoral factors were present in the normal drinking condition. In contrast, injections of 6 and 16 μg/kg BN produced the same pronounced suppression in salt intake in both the closed and open fistula test conditions. Only 16 μg/kg GRP was behaviorally effective, and this dose reliably suppressed both normal and sham drinking of salt. On an equimolar basis, BN was more potent than GRP. Injections of NMB had no effect on salt intake under any dose or fistula condition. The order of BN-like peptide potency in suppressing sham and normal drinking of salt by sodium-deficient rats (BN > GRP > NMB) is similar to the peptides' effects on feeding. When postoral feedback is minimized, the combination of BN or GRP and pregastric stimuli mimic the salt intake by rats in the fistula closed, normal drinking condition.

Rapid elicitation of salt appetite by an intravenous infusion of angiotensin II in rats.

A role for the renal renin-angiotensin system in the direct stimulation of salt appetite in the rat remains controversial because attempts to elicit the behavior by intravenous administration of angiotensin II (ANG II) have been unconvincing. We recently demonstrated that depletion-induced salt appetite was attenuated by selective blockade of peripheral ANG II synthesis with an intravenous dose of converting enzyme inhibitor [captopril (Cap)] that does not block the synthesis of ANG II inside the blood brain barrier. We now show that intravenous ANG II at 30 ng/min rapidly reestablishes salt appetite in Cap-blocked rats. The mean arterial blood pressure (MAP) of unblocked, sodium-depleted rats was normal, but Cap-blocked, depleted rats had low MAP. An intravenous infusion of ANG II in Cap-blocked rats brought MAP into the normal range and elicited water and salt drinking within 90 min. Phenylephrine also normalized MAP but failed to elicit fluid intake in Cap-blocked, sodium-deficient rats. Sodium and water balances tended to be more positive during ANG II than during phenylephrine infusions. Thus circulating ANG II may stimulate both thirst and salt appetite by a direct action on the brain and not by causing natriuresis or by raising the blood pressure.

2012 Parabrachial unit responses to taste stimuli in acutely sodium-deficient rats

We have used the evoked expression of the immediate early gene-encoded proteins (c-Fos, Fos B, Jun B, Jun D, c-Jun and Krox-24) to monitor sensory processing in the hindbrain structures of rats undergoing somatic inflammation. Experiments were performed on freely moving animals that did not experience constraints other than those imposed by the disease itself. Local injections of chemicals were used to cause subcutaneous inflammation of the plantar foot or monoarthritis by intracapsular injection. Labelling was studied at survival times that corresponded either to the time points of maximum labelling in the spinal cord (4 h for the subcutaneous model, 24 h and two weeks for the monoarthritis model) or at survival times that corresponded to the chronic phase of monoarthritis evolution (six, nine and 15 weeks). Controls consisted of freely moving, unstimulated animals. Basal expression was observed for all immediate early genes and in a variety of stuctures, but always remained moderate. All immediate early gene-encoded protein expressions except c-Jun were evoked, but except for c-Fos, and to a lesser extent Jun D, intensities of staining always remained faint. The following results will be mainly based on c-Fos expression, as this protein proved to be the most effective marker for all the survival times studied.Somatic pain evoked c-Fos expression in a subset of discrete subrogions of both the caudal medulla oblongata and transitional areas of the pontomesencephalic junction. In the caudal medulla oblongata, structures involved were the caudal intermediate reticular nucleus, the subnucleus reticularis dorsalis, the ventrolateral reticular formation and the lateral paragigantocellular nucleus. Structures involved at the pontomesencephalic junction level mostly included the superior and dorsal lateral subnuclei of the parabrachial area, the nucleus cuneiformis and the most caudal portions of the lateral central gray, also including the laterodorsal tegmental nucleus; labelling in other lateral subnuclei of the parabrachial area always remained moderate. Staining in the caudal reticular areas was evident only at short survival times (4 and 24 h survival times in subcutaneous and monoarthritis models, respectively). Staining in nuclei of the pontomesencephalic junction was evident in all cases except for the very long survival periods (six to 15 weeks) of monoarthritis. In all cases staining was bilateral with contralateral predominance with regard to the stimulated limb.The present work demonstrates that hindbrain stuctures involved in somatic pain processing can be effectively identified in behaving animals and that c-Fos is the most reliable activity marker in this case. The structures involved only partially overlap with those implicated in anaesthesia or visceronociceptive processing as demonstrated previously, thus suggesting that a certain degree of specificity could exist for some of them. Nuclei of the caudal medulla oblongata would be more involved in eliciting cardiovascular behaviours that acute pain elicits while nuclei of the pontomesencephalic junction would be more involved in mediating pain of inflammatory origin.

Tachykinin NK 3 receptor agonist blocks sodium deficiency-induced shift in taste reactivity

Intracerebroventricular (i.c.v.) injections of tachykinin NK 3 receptor agonists suppress NaCl intake by sodium deficient rats. The brief exposure, taste reactivity test was used to examine the effect of tachykinins on the immediate, oral reinforcing properties of NaCl (0.5 M) in sodium replete and sodium deficient male rats. In sodium replete rats, intraoral infusions of NaCl elicited a mixed response comprised of a similar number of ingestive and aversive responses following i.c.v. injections of saline and succinyl-[Asp 6,N-Me-Phe 8]substance P , (6–11), (SENK), a NK 3 receptor agonist. When sodium deficient, saline injected rats showed a reliable increase in ingestive and a decrease in aversive taste reactivity responses. Lateral i.c.v. injections of SENK blocked the shift in taste reactivity responses by sodium deficient rats, indicating that concentrated NaCl retained its aversive taste property.

Effects of experience with salty food on salt selection in adrenalectomized rats.

Sodium-deficient rats will seek out NaCl in food or solution and regulate their salt need. The question of this study is the extent to which salt-seeking behavior can be modified by long-term exposure to a high NaCl diet. Four female rats were divided into two groups: (1) animals that were fed lab chow with extra NaCl added during breeding, gestation, and until the offspring were weaned, the Experienced group, and (2) animals that ate only plain lab chow until weaning, the Inexperienced group. Food preference was measured in the offspring at age 28-29 and 41-42 days and them about half of each group were adrenalectomized and half sham operated. All animals had access to both plain and NaCl-enriched food and saline for 10 days postoperatively. The saline solution was removed and intake measured for an additional 8 days. Early experience with the high NaCl diet resulted in greater consumption of the NaCl-enriched food preoperatively and altered the pattern of intake following the removal of the saline solution postoperatively. The results indicate that early exposure to a high salt diet can influence the rats' later salt-seeking behavior.

Opioidergic manipulations affect intake of 3% NaCl in sodium-deficient rats

On six weekly occasions, a 3% NaCl solution was presented along with water to rats for 2 h 1 day after being treated with furosemide, a diuretic/natriuretic drug that causes a strong hunger for 3% NaCl. On some of the days, the sodium-hungry rats were injected with morphine in doses ranging from 0.3 to 10.0 mg/kg. Morphine produced biphasic effects on intake of 3% NaCl, with doses of 0.3–3.0 mg/kg increasing intakes dose dependently and 10.0 mg/kg decreasing intakes. The 3.0-mg/kg dose nearly doubled rats' mean intake of 3% NaCl. In contrast, naltrexone, an opioid receptor antagonists, reduced intake of 3% NaCl about 25–40% across doses ranging from 0.1 to 10.0 mg/kg. At some doses of morphine and naltrexone, NaCl ingestion was affected without significant influence of water intake. Therefore, it can be inferred that endogenous opioidergic systems participate in the control of NaCl drinking by sodium-deficient rats. The range of demonstrations of opioid involvement in the control of ingestion can now be extended to the hunger for hypertonic NaCl induced by sodium depletion.

Sodium deficient rats are unmotivated by sodium chloride solutions mixed with the sodium channel blocker amiloride.

Rats were made sodium deficient by furosemide injection and then offered 20 min of access to 0.05 M NaCl mixed with the sodium channel blocker amiloride. Compared with a sodium deficient control group that was also offered 0.05 M NaCl, these rats drank very little. A subsequent test conducted in the same manner with 20 min of access to 0.3 M NaCl mixed with amiloride produced similar results. It is concluded that amiloride blocks the neural information required for generating the attractive taste of NaCl to the sodium deficient rat.

Sodium deficient rats are unmotivated by sodium chloride solutions mixed with the sodium channel blocker amiloride.

Sodium deficient rats are unmotivated by sodium chloride solutions mixed with the sodium channel blocker amiloride.

Effect of Diet-Induced Sodium Deficiency on Normal and Compensatory Growth of the Lung in Young Rats

Sodium deficiency is associated with decreased muscle growth and protein synthesis. We investigated the influence of diet-induced sodium deficiency on the rate and extent of compensatory growth of the right lung after left pneumonectomy in young rats of 83 +/- 1 g body weight. Starting 1 wk before surgery, all rats were fed a diet deficient only in sodium (2-9 mumol Na+/g of food) ad libitum. Sodium-deficient rats were supplied with distilled water, whereas sodium-replete controls were supplied water containing 37 mM NaCl. After 7 d on the experimental diets, both groups were divided and subjected either to sham thoracotomy (Sham) or to left pneumonectomy (PNX). Somatic growth and both normal and compensatory growth of the lungs were assessed 3, 4, and 7 d later. Sodium-deficient animals grew more slowly than control animals. In control PNX rats, right lung weight to body weight ratio (LW/BW) increased to equal that of the combined LW/BW in control Shams by postoperative d 4, and remained at the Sham combined LW/BW value on postoperative d 7. Compensatory lung growth was less rapid in sodium-deficient PNX animals. At postoperative d 4, right LW/BW was low relative to combined LW/BW of sodium-deficient Shams. This ratio approached but did not reach the sodium-deficient Sham combined LW/BW value by d 7. Sodium deficiency thus reduced the rate of compensatory growth of the right lung.(ABSTRACT TRUNCATED AT 250 WORDS)