Elevated Plasma Osmolality Research Articles

The Role of the Renin-Angiotensin System in the Control of Blood Pressure and Drinking in the European Eel, Anguilla anguilla

The role of the renin-angiotensin system (RAS) in the control of blood pressure and drinking was investigated in fresh water (FW)- and seawater (SW)-adapted eels, Anguilla anguilla, by comparing the effects of pharmacological manipulation through the use of papaverine (stimulator) and captopril (inhibitor) on the endogenous system. In SW eels basal blood pressure levels were lower (23.3 ± 0.8 mm Hg) with correspondingly higher basal drinking rates (0.51 ± 0.07 ml/kg/hr) and plasma AII concentrations (32.89 ± 4.19 fmol/ml) compared to FW eels (33.8 ± 1.3 mm Hg, 0.06 ± 0.02 ml/kg/hr, 9.72 ± 0.60 fmol/ml, respectively). In FW eels papaverine caused immediate hypotension with full recovery, decrease in plasma osmolality, and increase in drinking rate and plasma AII concentration, but in SW eels, hypotension with full recovery and an increase in plasma osmolality. drinking rate, and plasma AII concentration occurred. In FW eels captopril had no effect on the parameters measured, but in SW eels it caused a sustained decrease in blood pressure and a decline in the basal drinking rate and plasma AII concentration. Papaverine was also administered 15 min after captopril In FW eels this manipulation caused hypotension only after the papaverine injection, followed by a partial recovery. Osmolality was unaffected, the previously observed papaverine-induced dipsogenic response was blocked, and the rise in plasma AII concentrations was smaller than with papaverine only. In SW eels there was an immediate hypotension after captopril administration with full recovery. The dipsogenic papaverine-induced response was blocked 90%, with elevated plasma osmolality and plasma AII concentrations compared to control values, although at a lower level compared to papaverine alone. A physiological role of RAS in the control of basal drinking in the SW eel is suggested.

Saline-Infusion-Induced Increases in Plasma Osmolality Do Not Stimulate Nasal Gland Secretion in the Ostrich (Struthio camelus)

Nasal gland activity was monitored in five freshwater and five saltwater-acclimated adult ostriches given an intravenous infusion of 1,500 mosm/kg sodium chloride for 90 min at 5 mL/min. The hyperosmotic infusion increased the plasma osmolality from 303.4 ± 6.9 to 353.3 ± 13.1 mosm/kg in the freshwater birds and from 299.4 ± 16.2 to 328.8 ± 15.4 mosm/kg in the saltwater-acclimated animals. None of the freshwater ostriches produced any observable nasal secretion. Two of the saltwater birds did show signs of glandular activity, but this was of short duration (5-10 min) and yielded insignificant volumes of fluid. The nasal glands of ostriches do not appear to play a quantitatively important role in the elimination of the administered saline load. Changes in plasma concentrations of arginine vasotocin (AVT) in response to the hyperosmotic infusion were also determined. Plasma AVT levels increased in parallel with the elevations in plasma osmolality (from 5.4 ± 0.9 to 19.4 ± 8.6 pg/mL in the freshwater ostrich...

Hemodialysis: relationship between signal intensity of the posterior pituitary gland at MR imaging and level of plasma antidiuretic hormone.

To investigate the correlation between signal intensity of the posterior pituitary gland on magnetic resonance (MR) images and levels of plasma antidiuretic hormone (ADH) in patients undergoing hemodialysis. The cases of 25 patients undergoing hemodialysis (15 men and 10 women, aged 24-75 years [mean, 51 years]) were prospectively evaluated. Laboratory testing and MR imaging were performed both before and after hemodialysis in 14 patients and only before hemodialysis in 11 patients. Before hemodialysis, nine patients (36%) had normal hyperintensity in the posterior pituitary gland, with almost normal plasma ADH levels and slightly elevated plasma osmolality. In six patients (24%) with less hyperintensity than is characteristic in the posterior pituitary gland, plasma ADH levels were slightly increased or normal. In 10 patients (40%) with an isointense posterior pituitary gland, plasma ADH and osmolality levels were evaluated. Elevated plasma osmolality may cause increased plasma ADH concentration and a lack of hyperintensity in the posterior pituitary gland at MR imaging.

Effects of dehydration, rehydration, and hyperhydration in the lactating and non-lactating black Moroccan goat

The effects of water deprivation, rehydration and hyperhydration were investigated in the black Moroccan goat ( Capra hircus). Mean daily water intake was 46 ± 5 ml/kg in lactating and 36 ± 4 ml/kg in non-lactating black Moroccan goats, and milk production 21 ± 1 ml/kg. Mean urine excretion was 8 ± 2 ml/kg body weight in both groups, and the daily water losses via evaporation and feces were estimated at 23 ± 3 ml/kg during lactation and 28 ± 4 ml/kg during non-lactation. Forty-eight hours of water deprivation caused a body weight loss of 9% and 6% in lactating and non-lactating goats, respectively, and a drop of 28% in milk production with only a slight decrease in food intake. After rehydration, the elevated plasma osmolality as well as Na and total protein concentrations returned to basal values within 2–3 hr, indicating a rapid absorption of the ingested water, but urine excretion did not increase. After hyperhydration (10% of body weight), 46% of the load was excreted by the kidneys within 6 hr. In conclusion, black Moroccan goats have a low water turnover, and they can retain water upon rehydration but not store excess water after hyperhydration.

Osmoregulatory changes in myo-inositol content and Na+/myo-inositol cotransport in rat cortical astrocytes.

Exposure of cortical astrocytes to 325, 350, or 390 mosM culture media for 48 h caused a 1.4-, 2.1-, and 3.5-fold increase, respectively, in cellular content of the compatible osmolyte myo-inositol. Elevated myo-inositol levels accounted for approximately 56-100% of the solute needed by the cells for complete volume regulation under hypertonic conditions. Myo-inositol accumulation was associated with 4-5-fold (peak rate) and 1.8-2-fold (steady-state rate) increases in the rate of Na(+)-dependent myo-inositol uptake when cells were acclimated to 390 mosM culture medium for 12 h or 24-96 h, respectively. When medium osmolality was elevated by 25 mosM, peak and steady-state increases in myo-inositol uptake of 1.7-fold and 1.3-fold, respectively, were observed. Exposure to 390 mosM medium for 12-48 h induced a 3-8-fold increase in cotransporter mRNA levels suggesting that the increase in myo-inositol uptake is brought about by increased cotransporter gene expression. Abrupt return of hypertonic cells to an isotonic medium induced a rapid increase in myo-inositol efflux and a return of cotransporter mRNA to control values in < 2 h. In contrast, the cotransporter remained fully activated at hypertonic levels for 16 h. Between 16-24 h after the transfer, the rate of myo-inositol uptake returned to control values. The remarkable sensitivity of the cotransporter to hypertonic stress indicates that upregulation of myo-inositol transport in glial cells is likely to occur in a variety of disease states that cause an elevation of plasma osmolality. Slow downregulation of the cotransporter may be responsible in part for the slow loss of myo-inositol and cerebral edema that occurs with too rapid correction of chronic plasma hypertonicity.

Epidermal growth factor as a diuretic in sheep.

1. Epidermal growth factor (EGF) has recently been shown to stimulate both polydipsia and polyuria and the aim of this study was to determine which was the primary response. Ewes received a continuous intravenous saline infusion (100 ml day-1) for 12 days (days 1-12) and EGF at doses of 0 (n = 6) or 10 micrograms h-1 (n = 6) over days 5-8. The supply of water was ad libitum during days 1-4 and 9-12, but was fixed at the pretreatment mean of days 1-4 for each ewe during days 5-8. 2. During the period of fixed water intake, the EGF-treated ewes experienced mild dehydration with elevated plasma osmolality, sodium, renin and arginine vasopressin (AVP) concentrations and slightly reduced plasma atrial natriuretic peptide (ANP) concentrations. 3. When the supply of water returned to ad libitum, the EGF-treated ewes increased their water intake by 105% (5.25 +/- 0.28 vs. 2.55 +/- 0.19 l day-1) and subsequently fluid balance was restored; plasma electrolyte and hormone responses also returned to normal. 4. This experiment demonstrates that EGF infused at a dose rate of 10 micrograms h-1 I.V. into sheep has a direct renal diuretic effect.

Osmoregulatory responses of glucous-winged gulls (Larus glaucescens) to dehydration and hemorrhage.

The effects of dehydration and hemorrhage on plasma ionic, osmotic, and antidiuretic hormone (arginine vasotocin) concentrations and of hemorrhage on salt gland secretion and glomerular filtration rate were evaluated in glaucous-winged gulls, Larus glaucescens. Dehydration for 24 h did not affect plasma ionic, osmotic or arginine vasotocin concentrations; 72 h dehydration significantly elevated plasma osmolality, plasma sodium and chloride concentrations, and plasma arginine vasotocin concentration, but did not affect plasma potassium concentration. Constant infusion of 0.8 mol.1-1 NaCl increased plasma arginine vasotocin concentration and produced salt gland secretion in seven gulls; four secreted well, while three secreted less well. Removal of 20% blood volume during saline infusion immediately reduced (P<0.001) salt gland secretion rate in all gulls. After bleeding, good secretors maintained glomerular filtration rate and urine flow rate; the poorer secretors increased glomerular filtration rate and became diuretic. Blood replacement returned salt gland secretion rate to the prebleeding level (P<0.05) without affecting salt gland secretions sodium concentration in gulls which secreted well, but did not restimulate salt gland secretion in gulls which secreted poorly. Reinfusion of blood had no effect on glomerular filtration rate. Bleeding and blood replacement did not affect plasma arginine vasotocin concentration.

Central oxytocin inhibition of salt appetite in rats: evidence for differential sensing of plasma sodium and osmolality.

Sodium chloride ingestion is stimulated during conditions of sodium deficiency to maintain body fluid and electrolyte balance. Recent studies have indicated that salt appetite in rats is often inversely related to peripheral and central secretion of the hormone oxytocin (OT). We studied the potential role of central OT on salt and water ingestion by treating rats intracerebroventricularly with OT conjugated to the A chain of the plant cytotoxin ricin (rAOT) to produce a chronic selective inactivation of brain cells containing OT-receptive elements. The rats treated with rAOT and control rats treated with the ricin A chain alone were given 5-hr two-bottle (water and 0.5 M NaCl) drinking tests 30 min after they were made hyperosmolar by injections of hypertonic (2M) mannitol solution, which elevated plasma osmolality but reduced plasma Na+ concentration. In the control rats only water intake was stimulated in response to the induced hyperosmolality, but in the rAOT-treated rats hypertonic mannitol caused a robust salt appetite as well as thirst. Analogous results were obtained in rats treated with two different OT-receptor antagonists prior to induction of hyperosmolality with mannitol. In contrast to these results, when hyperosmolality was induced by administration of equivalently hypertonic (1M) NaCl, which elevated both plasma osmolality and plasma Na+ concentration, only water intake but not salt intake was stimulated in both control and OT-receptor antagonist-treated rats. When salt appetite was stimulated by the physiological stimulus of polyethylene glycol-induced hypovolemia, hypertonic mannitol similarly inhibited salt ingestion in control animals but not in rAOT-treated rats, whereas hypertonic NaCl inhibited subsequent salt ingestion in both groups. These results suggest that salt appetite is regulated by both Na(+)- and osmolality-sensing mechanisms in rats. In addition, they indicate that central OT likely mediates a significant component of osmolality-related inhibition of salt appetite but does not appear to be essential for Na(+)-related inhibition of this important homeostatic behavior.

Inhibition of vasopressin and aldosterone release by atrial natriuretic peptide in conscious rabbits

To elucidate the regulatory role of atrial natriuretic factor (ANF) on vasopressin (AVP) and aldosterone release in conscious rabbits, ANF was administered systematically at a rate of 15 pmol min-1 (kg body wt)-1 for 15 min in two series of experimental animals in which AVP and/or aldosterone production was stimulated. In euhydrated rabbits (series I), systemic administration of angiotensin II (Ang II) (10 pmol min-1 (kg body wt)-1, 15 min) stimulated aldosterone release threefold from basal plasma concentrations (140 pg ml-1). The co-application of ANF inhibited the Ang II-induced release of aldosterone without influencing the non-stimulated AVP system. In dehydrated rabbits (series II) with elevated plasma osmolality and AVP concentration, exogenously applied ANF increased plasma ANF fourfold at marginally reduced arterial pressure. Plasma AVP concentrations were reduced by 3.4 pg ml-1 (25%) on average, and plasma aldosterone concentrations were lowered by 34 pg ml-1 (23%) at unchanged levels of plasma corticosterone. Receptor binding studies using [125I]ANF as radioligand revealed Ang II-independent high-affinity receptors for ANF in the zona glomerulosa of the adrenal gland. With regard to the hypothalamo-neurohypophyseal AVP system, ANF binding sites were localized to the median eminence and neurohypophysis, but not to the magnocellular nuclei. ANF receptors were also labelled in structures lacking a blood-brain barrier such as the subfornical organ and the choroid plexus.

Sex difference in blood pressure of spontaneously hypertensive rats influenced by perinatal NaCl exposure

Our prior study showed that the basal blood pressure level and pressor response to peripheral angiotensin II of adult Sprague-Dawley rats were enhanced by perinatal exposure to a high NaCl diet. The purpose of the present study was to assess further the relationship between NaCl-sensitivity of blood pressure and perinatal NaCl exposure. We tested the hypothesis that the basal blood pressure level and pressor responses to angiotensin II could be increased by perinatal exposure to high NaCl in NaCl-resistant spontaneously hypertensive rats (SHR-R). Adult female SHR-R were maintained on a diet containing either basal 1% or high 8% NaCl throughout pregnancy and lactation. The offspring were continued on these same diets to 30 days postpartum. Thereafter, all offspring were maintained on a diet containing 1% NaCl. After being adapted to restraint, systolic blood pressure was measured indirectly by the tail-cuff procedure when the rats were 30, 44, and 58 days of age. Subsequently, baseline mean arterial pressure (MAP) and pressor responses to intravenous administration of angiotensin II (20, 40, 80, and 120 ng/kg body weight) were obtained from the catheterized femoral artery in conscious unrestrained rats. The MAP levels of adult female SHR-R exposed perinatally to 8% NaCl were significantly greater than those of females exposed to 1% NaCl. This elevated blood pressure was accompanied by an elevation in plasma osmolality. Perinatal exposure to 8% NaCl did not raise the blood pressure and plasma osmolality levels of adult male SHR-R, but did enhance pressor responses to angiotensin II. On the basis of previous observations from other laboratories, we suggest that dietary NaCl manipulation during perinatal development modulates the sensitivity of central angiotensin II receptors and possibly central arginine vasopressin receptors and/or synthesis and release.

Participation of periventricular dopamine receptors in vasopressin secretion elicited by hypertonicity of systemic blood in rats

The aim of this study was to examine in conscious rats the role of periventricular dopamine receptors in vasopressin secretion caused by hypertonicity of the systemic blood. Intracerebroventricular injections of dopamine (0.15 or 0.75 mumol) produced dose-related increases in plasma AVP 90 sec or 5 min later, without affecting plasma osmolality, concentrations of electrolytes, hematocrit, arterial pressure or heart rate. The AVP response to 0.75 mumol dopamine was blocked by its antagonists, SCH 23390, sulpiride and haloperidol, given intracerebroventricularly at a dose of 0.15 mumol 10 or 40 min before the injection of dopamine. The ip injections (2 ml/100 g) of 600 mmol/l NaCl produced, 15 or 30 min later, augmentations in plasma AVP accompanied by elevations in plasma osmolality, sodium and chloride. At a dose of 0.15 mumol given intracerebroventricularly 10 min before the injection of 600 mmol/l NaCl, SCH 23390 or sulpiride inhibited the AVP response at 15 min, and sulpiride or haloperidol inhibited that at 30 min. The increases in plasma osmolality and the electrolytes owing to hypertonic saline were not reduced by these dopamine antagonists. The intracerebroventricular applications of the antagonists followed by those of vehicles for dopamine or by ip injections of 150 mmol/l NaCl were without any effect on plasma AVP or the other plasma variables. On the basis of these results, we concluded that dopamine receptors in the periventricular regions may contribute to AVP secretion in response to hypertonicity of the systemic blood.

Osmotic adaptation of the emu (Dromaius novaehollandiae)

1 The emu (Dromaius novaehollandiae) is well adapted to the Australian semi-desert, although it has a limited renal concentrating ability. One problem is the balance between the ability to resorb ions and water from ureteral urine during its reflux into the coprodeum and rectum (colon), and the rate of ureteral inflow. To elucidate this problem the osmotic and nutritional state of wild birds needs to be studied in order to integrate laboratory and field investigations. 2. This paper reports plasma values and the composition of gut contents from birds shot in the arid interior during the hot, dry summer. The wild birds showed little sign of osmotic stress with only marginally elevated plasma osmolality, and near-isotonic contents of the coprodeal/rectal segment (332±6 mOsm). Intestinal contents showed that the birds were feeding on berries of bushes with either a high (Rhagodia) or a low (Santalum) content of NaCl. The coprodeal/rectal concentration of Na+ and Cl- were high enough to permit solute-linked water flow. There was little sign of fermentation. 3. In vitro investigation in the Ussing chamber of isolated coprodeum and rectum epithelium revealed an inwardly directed current which was amiloride inhibitable and amino acid independent, suggesting electrogenic Na absorption of around 4 μmol·h-1·cm-2mucosal area regardless of the NaCl intake. 4. Based on previously determined transport parameters of the coprodeum/rectum epithelium (Dawson et al. 1985) and ureteral excretion rates of water and electrolytes (Dawson et al. 1991), it is concluded that the lower gut can resorb the major part of the water coming from the kidneys (and ileum) on both low and high NaCl intakes. The lower gut is most important in the xeric adaptation. The reason for the apparently high transport capacity, larger than in other birds, of the lower gut (serosal area) was a high degree of folding of the mucosal surface (increasing surface area by factor of five).

Plasma vasopressin response to contrast medium during cardiac catheterization in infants and children

Fifteen infants and children (M = 7, F = 8), aged from 0 to 13 years, who underwent cardiac catheterization and cardioangiography under ketamine-diazepam anesthesia were the subjects of this study. The effect of a contrast medium, isolamate sodium (66.8%) on the plasma somolality and vasopressin concentration was studied. The plasma osmolality was significantly elevated after contrast medium administration (289 +/- 3 vs. 303 +/- 8 mosmol.kg(-1)) as well as plasma vasopressin (from 2.1 +/- 0.9 vs. 4.7 +/- 2.0 micro-unit.ml(-1)). It is concluded that the administration of contrast medium for cardioangiography causes elevation of plasma osmolality, which leads to the elevation of plasma vasopressin concentration.

Inhibition of elevated arginine vasopressin secretion in response to osmotic stimulation and acute haemorrhage by U‐62066E, a κ‐opioid receptor agonist

1. The effect of kappa (kappa) opioid receptor activation on the increase in arginine vasopressin (AVP) secretion evoked by two acute and quite different stimuli (i.e., haemorrhage and osmotic stimulus due to hypertonic saline infusion) were evaluated in conscious Long-Evans rats, by use of U-62066E, a highly selective kappa-opioid receptor agonist, and MR2266, an opioid receptor antagonist with some selectivity for kappa-receptors. 2. An acute haemorrhage, which reduced the mean blood pressure by approximately 50%, resulted in a large increase in the plasma AVP (pAVP) levels of control rats. However, the administration of U-62066E (0.2 mg kg-1 or 2.0 mg kg-1) reduced the increase due to haemorrhage in a dose-dependent manner. In contrast, concomitant administration of 2.0 mg kg-1 of MR2266 with U-62066E significantly attenuated the inhibition of pAVP levels produced by U-62066E 2.0 mg kg-1. 3. Hypertonic saline infusion (5% hypertonic saline solution at a rate of 0.24 ml kg-1 min-1 for 10 min) caused the elevation of plasma osmolality (pOsm) from 294.0 +/- 1.6 mosmol kg-1 to 304.4 +/- 1.9 mosmol kg-1, simultaneously resulting in a significant increase in pAVP levels from 2.34 +/- 0.28 pg ml-1 to 4.54 +/- 0.51 pg ml-1. However, the administration of U-62066E (0.05 mg kg-1 or 0.2 mg kg-1) reduced the osmotically induced increase in pAVP in a dose-dependent manner although pOsm showed the same degree of increase as in controls. In contrast, concomitant administration of 0.2mgkg-1 of MR2266 with U-62066E significantly attenuated the inhibition of pAVP levels produced by U-62066E 0.2mgkg- , whereas pOsm showed the same degree of increase as in controls. No significant changes in the mean blood pressure of the respective groups were observed during this experiment. 4. It is suggested that the Kappa-Opioid receptor activation reduces the increase in AVP secretion evoked by these two different stimuli and that the inhibitory involvement occurs in the neural lobe in the process of AVP secretion.

Neuropeptide Y (NPY) and vasopressin (AVP) in the hypothalamo-neurohypophysial axis of salt-loaded or Brattleboro rats

A close anatomical relationship between nerve terminals containing neuropeptide Y (NPY) and vasopressin (AVP) has been demonstrated in the hypothalamic paraventricular (PVN) and supraoptic nuclei (SON). Furthermore, injections of NPY into the SON increased plasma concentrations of AVP in the rat. These data suggest a potential involvement of hypothalamic NPY in fluid homeostasis in the rat. Therefore, we have studied the effect of elevated plasma osmolality on the concentration of NPY and AVP in the hypothalamus and neurointermediate lobe (NIL) of the pituitary gland. Furthermore, we measured the concentration of NPY in the AVP-deficient Brattleboro rat, which suffers from diabetes insipidus and hyperosmolality. Salt-loading increased plasma osmolality and the concentration of AVP from2.0 ± 0.5to4.1 ± 0.6pg/ml after 7 days. The concentration of NPY in the NIL doubled after 7 days of salt-loading, from7.9 ± 0.6ng/mg protein to15.2 ± 1.4ng/mg protein, whereas AVP concentrations fell from2285.7 ± 210.9ng/mg protein to187.5 ± 2.5ng/mg protein. AVP concentrations in the ME increased transiently after 2 days of salt-loading and returned to control levels after 7 days. In contrast, NPY concentrations in the ME were unchanged at 2 days and were increased 61% after 7 days. NPY concentrations also were significantly elevated after 7 days of salt-loading in the preoptic area (POA) and mediobasal hypothalamus (MBH). The concentration of NPY in the NIL of the homozygous Brattleboro rat was 2-fold greater than in the heterozygous Brattleboro rat and 4-fold greater than in Sprague-Dawley rats used as controls. Additionally, the concentration of NPY in the POA and MBH was higher than in control animals. These studies show that NPY concentrations in the hypothalamo-neurohypophysial axis are responsive to changes in fluid balance and raises the possibility that NPY may play a physiological role in the modulation of AVP secretion in the rat.

Renal tubular vasopressin receptors downregulated by dehydration.

Receptors for arginine vasopressin (AVP) were characterized in tubular epithelial basolateral membranes (BL membranes) prepared from the kidneys of male Sprague-Dawley rats. Association of [3H]AVP was rapid, reversible, and specific. Saturation studies revealed a single class of saturable binding sites with a maximal binding (Bmax) of 184 +/- 15 fmol/mg protein and a KD of 0.61 +/- 0.04 nM. IC50S for AVP, lysine vasopressin, and oxytocin were 0.74 nM, 9.7 nM, and greater than 1 microM, respectively. The V2 receptor antagonist was more than 3,700 times as effective in displacing [3H]AVP than was the V1 antagonist. To investigate the physiological regulation of vasopressin receptors, the effects of elevated levels of circulating AVP on receptor characteristics were studied. Seventy-two-hour water deprivation significantly elevated plasma osmolality and caused an 11.5-fold increase in plasma [AVP]. Scatchard analysis revealed a 38% decrease in the number of AVP receptors on the BL membranes from dehydrated animals. The high-affinity binding sites on the BL membranes fit the pharmacological profile for adenylate cyclase-linked vasopressin receptors (V2), which mediate the antidiuretic action of the hormone. We conclude that physiologically elevated levels of AVP can downregulate vasopressin receptors in the kidney.

Salt and water intake in Brattleboro rats with hypothalamic diabetes insipidus

Brattleboro rats lacking vasopressin have an elevated plasma osmolality and a stimulated renin-angiotensin system relative to Long-Evans rats (LE). The current studies were performed to elucidate the factors controlling water and salt intake in the Brattleboro rat with diabetes insipidus (DI). DI and LE rats were (1) given the choice of water and saline solutions ranging from 0.1–1.0% to assess palatability, (2) dialyzed with isotonic glucose to test for sodium appetite after sodium depletion, and (3) infused intracranially with an angiotensin II analogue (saralasin) to assess the role of angiotensin II in spontaneous salt and water intake. DI rats exhibited spontaneous salt intake which was not significantly different from LE rats and increased their intake of 3.0% NaCl following sodium depletion, although less reliably than LE rats. A significant proportion of those DI rats not developing a sodium appetite showed attenuation of their diabetes following dialysis. No evidence for involvement of angiotensin II in spontaneous salt and water intake was found.

Drinking and natriuresis during volume expansion and intracranial angiotensin or carbachol

Two methods of sodium loading were used to counteract the body fluid dilution resulting from natriuresis and water drinking during sustained lateral ventricular infusions of carbachol (CBC) or angiotensin II (ANG II) in rats. It was expected that preventing dilution would also prevent the precipitous decline of both drinking and natriuresis during the later hours of CBC infusion. In the first study, rats having isotonic saline as the sole drinking fluid during CBC infusions drank less fluid and had only slightly higher plasma osmolality and sodium concentration than rats drinking water, which showed extreme dilution. In the second study, rats with only water to drink were given intravenous infusions of 0.15, 0.45, or 1.00 M NaCl solutions at 1.8 ml/h concurrently with the intraventricular infusions. Significant dilution of plasma was found at the two lower rates but not at 1.00 M NaCl in CBC-infused rats. Only the latter group showed both persistent drinking and natriuresis throughout the 4-h infusion period, and this was not because of elevated plasma osmolality. Infusions of ANG II generated less severe body fluid dilution and more persistent drinking in both experiments. The study demonstrates that body fluid dilution may control the offset of both drinking and natriuresis during sustained infusions of CBC and that the more persistent drinking to ANG II vs. CBC probably occurs because of a lesser natriuresis and consequent fluid dilution.

Effects of acute hyperosmolar NaCl or urea on brain H2O, Na+, K+, carbohydrate, and amino acid metabolism in weanling mice: NaCl induces insulin secretion and hypoglycemia.

This study compares early and late effects of the injection of hyperosmolar NaCl and urea of equal osmolarity on selected aspects of brain water, electrolyte, carbohydrate, amino acid, urea, and energy metabolism in normal suckling-weanling mice. One hour after treatment, salt-treated mice were critically ill, while the behavior of urea-treated animals could not be distinguished from that of controls. This clinical difference could not be explained on the basis of differences in plasma osmolality, the brain water content, or the degree of hemorrhagic encephalopathy. The injection of NaCl induced a 14-fold increase in plasma insulin and a progressive fall in the plasma glucose concentration (a reduction of 66% at 1 hr). In contrast, plasma glucose levels in urea-injected mice were unchanged. Prior to the fall in plasma glucose levels, metabolite changes in the brains of NaCl-injected mice were compatible with facilitation of transfer of glucose from the blood to the brain, increased metabolic flux in the Embden-Meyerhof and Krebs citric acid cycle pathways, and increased energy production. With the exception of the glucose content (unchanged), similar metabolite changes were seen in brain soon after urea injection. In the brains of the hypoglycemic NaCl-treated mice, glucose levels were reduced 80%, and glycogen 41%. Other metabolite changes were compatible with decreased glycolysis and metabolic flux through the Krebs citric acid cycle. In contrast, with few exceptions, at a similar time after injection, metabolite levels had returned to normal in the urea-treated mice. Permeability of the brain to urea was also examined. Brain urea reached high levels at 2 hr but returned to near baseline at 6 hr. Both hyperosmolar solutions increased the brain content of aspartic and glutamic acids 1 hr after injection. The failure of hypoglycemic mice with hypernatremia and elevated plasma osmolality (range, 416-434 mOsm/kg H2O) to respond to 1 M glucose (30 ml/kg) may have been due to the ill effects of the additional hyperosmolar load. The possibility remains that the encephalopathy induced by hyperosmolar NaCl, but not by hyperosmolar urea, is in some way related to the sudden elevation of brain Na+ and/or Cl- ions.

Characterization of a new rodent model of diabetes insipidus: the Roman high avoidance rat homozygous for diabetes insipidus.

These experiments were designed to characterize the nature and extent of diabetes insipidus present in a new model of genetic vasopressin (VP) deficiency, the Roman high avoidance rat homozygous for diabetes insipidus (RHA: di/di strain). The new strain was developed from an initial cross between Long-Evans derived Brattleboro (LE:di/di) rats and normal Roman high avoidance (RHA: +/+) rats, and has been bred to be congenic with the parent RHA: +/+ strain. RHA: di/di rats exhibited polydipsia, excreted dilute urine, and exhibited elevated plasma osmolality. RHA: di/di rats shows a similar urinary response to dehydration as LE: di/di rats. VP was undetectable by radioimmunoassay in the serum, brain, and neurohypophysis of RHA: di/di rats. VP-neurophysin containing cells were not observed in the brains of RHA: di/di rats upon immunocytochemical analysis. Thus, the new RHA: di/di strain exhibits essentially the same profile of diabetes insipidus as the LE: di/di rat. The congenic relationship between RHA: di/di and RHA: +/+ rats makes the RHA: di/di rat a useful model under circumstances where genetic variables unrelated to VP deficiency may confound the interpretation of data.