The relationship between urinary prostaglandin excretion rates and urine flow in conscious rats. Evaluation of the radioimmunoassay by gas chromatography-mass spectrometry

In conscious rats prostaglandin E2- and F2 alpha excretion rates increased from about 20 to more than 100 pg/min/g kidney weight as urine flow decreased from about 10 to below 1 microliter/min/g kidney weight following 24 h of water deprivation confirming previous data from surgically prepared rats (Leyssac & Christensen 1981 b). There was no difference in this response between rats on a normal sodium diet and severely sodium depleted rats. Additional supply of polyunsaturated fatty acids in the food did not influence the results. Elevated levels of prostaglandin excretion did not correlate with urine osmolality. The reliability of the radioimmunoassays used was documented by comparison with measurements by gas chromatography-mass spectrometry. The analysis showed that these two methods provide almost identical estimates of urinary PGE2 and PGF2 alpha content. It is concluded that renal prostaglandin production is activated by a negative feedback mechanism as tubular and/or urine flow rate decreases towards subnormal values.     

Responses of Reindeer to Water Loading,Water Restriction and ADH

Two female reindeer were hydrated by administration of (10% of b.wt.) water into the rumen. The diuretic response was very fast and strong but the urea and electrolyte excretion were little affected. Dehydration was carried out by not giving the reindeer water for 48 h. This water deprivation caused a loss of up to 20% of their body weight. The urine osmolality did not exceed 840 mosm/kg H₂O, although the plasma osmolality rose from 300 to 346 and 368 mosm/kg H₂O respectively. The plasma and urine urea concentrations were elevated during dehydration, while the urine urea excretion did not increase. Urine sodium concentration did not increase. When the urine flow rate, after two days of water deprivation, decreased to half of the original, the urine Na⁺ concentration, instead of increasing, went down to half of the original. So did the potassium excretion. When ADH was injected intravenously into hydrated animals a dose of 30 mU of ADH was needed to induce antidiuresis or increased excretion of potassium. The resistance to ADH and the low relative thickness of the medulla confirm the limited capacity of reindeer kidney to concentrate urine or to excrete a solute load. On the other hand, reindeer is able rapidly to excrete surplus water without affecting the electrolyte or nitrogen balance.     

Water deprivation-induced drinking in rats: role of angiotensin II

The role of angiotensin II in the control of water intake following deprivation of water for varying lengths of time was studied. Male rats were deprived of water for 0, 12, 24, 36, or 48 h. Water intakes were measured with and without pretreatment with the angiotensin I-converting enzyme inhibitor, captopril (50 mg/kg, ip). Captopril had no significant effect on water intake following either 0 or 12 h of water deprivation. However, captopril significantly attenuated water intake following 24-48 h of water deprivation with the magnitude of the attenuation increasing as the length of the period of water deprivation increased. Plasma renin activity was significantly increased over control levels after 24-48 h of water deprivation but not after 12 h of water deprivation. Plasma renin activity tended to increase as the length of the water-deprivation period increased. Serum osmolality and sodium concentration were significantly increased over control levels following 12-48 h of water deprivation. Serum osmolality and sodium concentration failed to show any further increases with increasing length of water deprivation beyond the increases following 12 h of water deprivation. The data indicate that the water intake of water-deprived rats can be divided into an angiotensin II-dependent component and angiotensin II-independent component. The angiotensin II-independent component appears to be more important in the early stages of water deprivation whereas the angiotensin II-dependent component becomes more important as the length of the water-deprivation period increases.     

Lesions of the MPO or AV3V: influences on fluid intake

Electrolytic lesions in the MPO of rats had no significant effects on ad lib food and water intake, but impaired the drinking response to 1 M NaCl. Large MPO lesions also produced a persistent increase in plasma osmolality. In Experiment 2, we depleted neurons from the MPO of rats by iontophoretic application of the neurotoxin kainic acid (KA) which destroys nerve cell bodies without damage to fibers of passage. KA-induced neuron depletion in the MPO of rats significantly reduced the drinking response to 1.0 M saline, to 30% PG, and to 30 micrograms/kg isoproterenol. Ad lib water intake and drinking responses to food or water deprivation, to low concentrations (0.5 M) of hypertonic saline, to low concentrations (10% or 20%) of PG, and to systemic administration of 1.5 mg/kg angiotensin II were within the normal range. In Experiment 3, rats with electrolytic lesions that were strictly confined to the tissue immediately surrounding the wall of the anteroventral portion of the third ventricle (AV3V), without invading the MPO displayed normal ad lib food and water intake and plasma osmolality as well as drinking responses to water deprivation, hypertonic saline (0.5 or 1.0 M), angiotensin II (1.5 mg/kg) and isoproterenol (30 micrograms/kg).     

Drinking in the pigeon (Columba livia) in response to water deprivation and the influence of intracerebroventricular infusions of NaCl or sucrose solutions

Pigeons were deprived of fluid for 24 hours then allowed access to water and a 2.7% NaCl solution, the intakes of both solutions during the subsequent 60 min were observed. In a second experiment hypertonic or isotonic solutions of NaCl or sucrose were infused ICV, starting 5 min before access to the solutions and finishing 10 min after access, and the consummatory behaviour observed. Pigeons rehydrated themselves after the period of deprivation with a volume of water equal to the weight lost during the deprivation. Pigeons never drank the hypertonic NaCl solution. ICV infusions of hypertonic or isotonic sucrose attenuated drinking in response to 24 hours water deprivation. Isotonic or hypertonic NaCl infused ICV, on the other hand, had no significant effect. Thus, in the pigeon, drinking in response to 24 hours of water deprivation appears to be controlled by one mechanism, possibly osmoreceptor in nature (with the permissive control of CSF sodium concentration), since the birds drank a volume of water equal to their weight loss and changes in CSF sodium concentration influenced drinking in a manner similar to that described previously for osmotically induced drinking in pigeons.     

Effect of water deprivation on urinary excretion of PGE2 in the dog

We examined the influence of the state of hydration on the urinary excretion of prostaglandin E2 (PGE2) and kallikrein in the dog. Immunoreactive PGE2 and kallikrein were measured in the urine of conscious dogs during periods of water deprivation and periods of free access to drinking water and in the urine of time-control dogs that had free access to water throughout the study. During water deprivation the excretion of kallikrein did not change significantly, but PGE2 excretion increased by 50 and 75% (P less than 0.05) after 2 and 4 days, respectively, associated with reductions of body weight and urine flow and with elevation of plasma renin activity, plasma sodium, and both plasma and urine osmolality. Dehydrated dogs drank copiously when allowed free access to water, and over the following 4 days both PGE2 excretion and plasma renin activity fell significantly, associated with elevation of body weight and urine volume and with lowering of plasma sodium and plasma and urine osmolality. In contrast, if after 4 days of water deprivation the dogs were kept at a constant level of dehydration by restricting their water allotment on subsequent days to 300 ml/day, PGE2 excretion and most other variables remained at the dehydration level. In conclusion, these results suggest that renal PGE2 production is dependent on the state of hydration in the dog.     

Renal involvement in active `juvenile' cirrhosis

Twelve patients with active `juvenile' cirrhosis (active chronic hepatitis, `lupoid' hepatitis) and six subjects with other types of portal or postnecrotic cirrhosis were submitted to percutaneous renal biopsy. In addition, renal function was assessed in all patients by measurement of the 24-hour endogenous creatinine clearance, maximal urinary osmolality after deprivation of water, 24-hour urinary protein excretion, and routine urine analysis.     

Effects of fluid intake on basal and vasopressin-responsive urinary prostaglandin E

The effects of fluid intake on basal and vasopressin-responsive urinary PGE excretion (UPGEV) were examined in conscious rats under conditions of 1) ad libitum water intake, 2) water deprivation, and 3) water diuresis induced by ad libitum intake of 5% dextrose in water. UPGEV fell progressively during 40 h of water deprivation. Water diuresis after water deprivation increased UPGEV transiently (8 h). Vasopressin (Pitressin tannate in oil, 5 U/kg subcutaneously) increased UPGEV and decreased urine volume (V) in rats on ad libitum water intake but did not alter UPGEV during water deprivation. Indomethacin suppressed UPGEV (70-90%), increased basal urine osmolality (Uosmol), and potentiated the antidiuretic response to Pitressin in rats on ad libitum water intake. Indomethacin accelerated by 8 h the onset of maximal antidiuresis in water-deprived rats but did not significantly alter water balance. During water diuresis, UPGEV declined in the first 8 h after Pitressin. Thereafter, UPGEV increased markedly, concurrent with early vasopressin escape. Indomethacin or meclofenamate inhibited the rise in UPGEV, the decline in Uosmol, and the increase in V of the escape phase. Indomethacin or meclofenamate also impaired the excretion of an acute water load (5% body wt) given during escape. The spontaneous decline in UPGEV during hydropenia may serve to maximize physiologic antidiuresis. Conversely, the marked increase in UPGEV induced by administration of vasopressin during water diuresis may serve to suppress the antidiuretic response and thus play a role in the mediation of escape from physiologically inappropriate antidiuresis.     

Deviations in body fluids during fasting in rats: failure of ADH treatment and nonnutritive bulk in preventing the occurrence of plasma hypovolemia

During fasting rats initially exhibited a slight plasma hypervolemia followed by hypovolemia, with an accompanying increase in plasma osmolality, which became more severe as food deprivation continued. Urinary sodium, potassium and chloride concentrations were depressed with deprivation and this condition persisted through the six days of fasting examined. Urine osmotic pressure indicated a recovery trend by the fourth day of deprivation. This temporally coincided with a marked reduction in water consumption. In a second experiment Pitressin treatment increased urine osmolarity during four days of food deprivation, but urinary sodium and potassium concentrations were not changed nor was the plasma hypovolemia influenced. In the third experiment nonnutritive bulk in the form of Vaseline-cellulose mixture was ingested by both rats and gerbils during starvation. Water consumption and urine volume were decreased by such bulk ingestion, however, the urine remained dilute as compared with ad lib levels, and the plasma hypovolemia persisted.     

Water and sodium movements across the ruminal epithelium in fed and food-deprived sheep

Fluid and electrolyte movements across the ruminal epithelium of sheep were studied using the temporarily isolated rumen technique. The sheep were all subjected to the following treatments: (1) fed sheep (fed twice daily), after rumen emptying, received rumen contents from a fed sheep; (2) food-deprived sheep (two meals were omitted), after rumen emptying, received rumen contents from a food-deprived sheep; (3) fed sheep, after rumen emptying, received rumen contents from a food-deprived sheep; and (4) food-deprived sheep, after rumen emptying, received rumen contents from a fed sheep. Food deprivation led to an increased Na concentration of the rumen fluid while K and Cl concentrations, as well as osmolality, decreased. Plasma Na and osmolality decreased. During the 40 min after the rumen contents were exchanged no net movements of water occurred. Then the sheep were given an intraruminal load of saline which gave rise to a significant net absorption of fluid from the rumens of those sheep which had received rumen contents from fed sheep. The change in composition of the rumen contents after food deprivation impaired the absorption of Na and water from the rumen. Furthermore food deprivation reduced the Na absorptive function of the ruminal epithelium, but not the water permeability.     

Food and water intake and weight regulation in the pigeon

The interaction of eating and drinking and the relation between intake and body weight was examined in pigeons maintained under laboratory conditions in order to obtain normative data on intake and weight regulation in this species. Under ad lib conditions food and water intake values are correlated, while deprivation of either nutrient leads to a reduction in the intake of the other. A linear relation between the log food intake and the log body weight was found under both ad lib and deprivation conditions. Following a period of food deprivation the pigeon shows both a short-term and a long-term compensatory increase in food intake whose magnitude is directly proportional to the degree of body weight loss produced by deprivation. The findings for the pigeon are similar in many respects to those reported for the rat and are discussed in relation to weight regulation and motivational mechanisms in hunger and thirst.     

红细胞在保护剂添加和洗涤时的非平衡渗透响应实验研究

在红细胞低温保存或冻干保存中，高浓度保护剂的添加和洗涤会使细胞体积收缩或膨胀，造成溶血损失，但其体积并非单调收缩或膨胀到最后平衡体积，而是要经历更严重的体积变化后再趋于平衡。本研究以NaCl溶液来模拟保护剂的添加与洗涤过程．将38种不同浓度的NaC;溶液，以一步直接法、4步等体积法或4步等摩尔浓度变化法添加到红细胞中，测定其溶血率。若以溶血率10％为标准，红细胞所能承受的最小渗透压在161mOsmol／k附近，而最大渗透压与溶液添加方式有关，等体积添加法效果较好（其值约为5680mOsmol／kg）。研究中还将12％、18％NaCl溶液以4步等体积法加到红细胞中，再用生理盐水以三种方式洗涤，发现等摩尔浓度变化法洗涤效果最好；洗涤后溶血率大大增加，说明很多细胞虽然在保护剂添加时未溶血，但膜脆性已改变，难以恢复到等渗时体积。     

Urinary concentrating ability during dehydration in the absence of vasopressin.

Despite the apparent absence of vasopressin (ADH), Brattleboro homozygotes [diabetes insipidus (DI) rats] can concentrate their urine when deprived of drinking water. Since other investigators have shown that reducing glomerular filtration rate (GFR) improves the concentrating ability of water-loaded dogs, the present studies were undertaken to quantify the magnitude and time course of changes in GFR during dehydration. Clearance experiments were performed in 10 conscious DI rats before and following 3, 6, 9, 12, 15, and 24 h of dehydration. Urine osmolality increased from 155.0 +/- 12.6 (SE) to 696.7 +/- 8.4 mosmol/kg H2O after 24 h. GFR averaged 984.3 +/- 79.6 microliters . min-1 . 100 g body wt-1 in the control phase, fell to about 80% of this value over the first 12 h of dehydration, and then declined to 27% at 24 h. The rats lost 20% of their body weight over the 24 h. The osmolality of the papillary tip averaged 896 +/- 44 mosmol/kg H2O at 24 h compared to a control value of 493 +/- 28. The lack of osmotic equilibration between urine and papillary interstitium suggests that dehydration did not appreciably increase the water permeability of the distal nephron. These experiments clearly show a progressive decline in GFR as urine becomes concentrated during dehydration in the absence of ADH; these events may or may not be causally related.     

Food deprivation decreases vasopressin mRNA in the supraoptic and paraventricular nuclei of the hypothalamus in rats

We examined the effect of food deprivation for three days on hypothalamic arginine vasopressin (AVP) mRNA in rats. Simultaneously the effect of water deprivation for the same period was examined as a model of dehydration. Levels of AVP mRNA in the supraoptic nucleus (SON) and the paraventricular nucleus (PVN) were determined by semiquantitative in situ hybridization histochemistry. Water deprivation increased AVP mRNA in both nuclei as previously reported. In contrast, food deprivation decreased AVP mRNA in these nuclei. The changes in AVP mRNA levels in the PVN were observed in the magnocellular subdivision of the nucleus. Plasma levels of ACTH and corticosterone were greatly increased in both treated groups of rats. Plasma AVP and osmolality levels were significantly elevated in water-deprived rats but not in food-deprived rats. These observations indicated that both food deprivation and water deprivation stimulated the pituitary-adrenal axis and that a reduction in AVP mRNA levels in food-deprived rats was caused by food deprivation but not by glucocorticoid feedback suppression nor by altered plasma osmolality.     

Role of rumen fluid hypertonicity in the dehydration-induced hypophagia of cows

Three experiments were performed in non-lactating, rumen-fistulated cows to assess the role of rumen fluid hypertonicity in dehydration-induced hypophagia. First, the course of rumen fluid and plasma osmolality before and after an individual test meal was recorded when water was offered ad libitum and on the fifth day of a 65% water restriction period. Then, the effects of intraruminal water infusions on food intake were examined in dehydrated cows. Finally, two doses of the local anesthetic mepivacaine HCl were given into the rumen in an attempt to inactivate the osmosensors potentially involved in dehydration-induced hypophagia. Water restriction reduced test meal size and increased rumen fluid and plasma osmolality. Despite the smaller meal, the prandial increase in rumen fluid osmolality was more pronounced during water restriction than with water ad libitum. Independent of treatment, the test meal had no effect on plasma osmolality. Intraruminal water infusions during water deprivation decreased rumen fluid osmolality below the control level and normalized food intake. Injection of 2 or 4 g mepivacaine/cow into the rumen did not attenuate dehydration-induced hypophagia. All in all, these results suggest that rumen fluid hypertonicity, perhaps in concert with plasma hypertonicity, contributes to the early satiation induced by dehydration.     

Plasma vasopressin in hereditary cranial diabetes insipidus

A family comprising 46 members of 4 generations is described; 21 members suffered from incomplete diabetes insipidus (DI) of central origin. The pedigree showed a dominantly transmitted condition. The onset is gradual and starts in early infancy. The clinical symptoms are highly variable and decline in the sixth decade. Plasma vasopressin (AVP) during water deprivation was significantly lower in the DI group than in the controls (4.2 +/- 0.5 vs. 10.6 +/- 1.7 ng/l) (p less than 0.01), the difference being more pronounced in the high osmolality range (4.8 +/- 0.7 vs. 14.4 +/- 3.1 ng/l) (p less than 0.01). Urine osmolality was lower (241 +/- 36 vs. 928 +/- 46 mOsm/kg H2O) (p less than 0.01) despite higher serum osmolality during water deprivation, rendering the ratio between urine and serum osmolality less than unity compared with greater than 3:1 in the control group (p less than 0.001). In two affected females, addition of a non-osmotic stimulus caused no increase in plasma AVP. The findings are consistent with a partial defect in the production or release of AVP and not with a dysfunction of the intracranial osmoreceptors. The variable features of incomplete DI indicate that to define the condition by excessive urinary output alone is insufficient. The ratio between urine and serum osmolalities after an appropriate osmotic stimulus together with plasma AVP measurements may be necessary to confirm the diagnosis.     

Amelioration of polyuria by amiloride in patients receiving long-term lithium therapy

Vasopressin-resistant diabetes insipidus is a common side effect of the treatment of affective disorders with lithium. We studied the effect of amiloride on lithium-induced polyuria in nine such patients receiving maintenance lithium therapy who had a vasopressin-resistant defect in urinary concentrating ability. After a mean (+/- S.E.) of 24 +/- 6 days of amiloride administration, the urine volume fell (from 4.7 +/- 0.6 to 3.1 +/- 0.3 liters per 24 hours; P less than 0.005), and the urine osmolality increased (from 228 +/- 35 to 331 +/- 34 mOsm per kilogram of H2O; P less than 0.001). The decrease in urine output was sustained during six months of observation in the absence of any significant change in plasma levels of lithium, potassium, or bicarbonate; urinary excretion of sodium or lithium; or creatinine clearance. Amiloride administration was also associated with a significant increase in urine osmolality (from 575 +/- 54 to 699 +/- 48 mOsm per kilogram of H2O; P less than 0.005) measured after fluid deprivation and the injection of exogenous vasopressin. We conclude that amiloride mitigates lithium-induced polyuria, at least partly, by blunting the inhibitory effect of lithium on water transport in the renal collecting tubule. Thus, amiloride may provide a specific therapy for polyuria in lithium-treated patients while obviating the need for potassium supplementation in the treatment of this kind of polyuria.     

Effects of lithium on circadian cycles in food and water intake,urinary concentration and body weight in rats

Circadian cycles in food and water intake, urinary concentration and body weight were studied in normals rats, lithium-polyuric rats, rats with hereditary diabetes insipidus, and rats infused continuously with arginine vasopressin (ADH) 10 mU/hr IV. Normal rats showed characteristic cycles in body weight and urine flow and osmolality with diuresis in the dark (eating and drinking period) and antidiuresis in the light (resting) period. ADH-infusion eliminated the circadian cycle in urine osmolality, but not in urine flow, suggesting that factors besides ADH mediate the antidiuresis during the resting period. Rats with ADH-deficient diabetes insipidus showed obliteration of all circadian cycles studied, indicating the importance of the renal concentrating mechanism for the amplitude of the circadian cycles, observed in normal rats. In rats treated with lithium, circadian cycles in body weight and urine osmolality were absent. However, there was a significant circadian variation in urine flow and food and water consumption with peak values during the light period, when normal rats showed minimal values. It is concluded that in rats lithium causes marked changes in circadian cycles, which probably cannot be explained by its effect on the renal concentrating mechanism alone.     

Protective effect of mannitol, glucose-fructose-sucrose-maltose mixture, and natural honey hyperosmolar solutions against ethanol-induced gastric mucosal damage in rats.

BACKGROUND: We have previously shown that natural honey is able to protect the rat stomach against acute ethanol- and indomethacin-induced lesions. The present investigations were undertaken to examine the role of intraluminal osmolality in this protective effect. METHODS: Mannitol, glucose-fructose-sucrose-maltose mixture (GFSM) and natural honey (300, 600, 1800 mOsmol/kg water) were given orally to rats 30 min before administration of 70% ethanol for a further 15-min period. Lesions area of the excised stomachs were evaluated. Pylorus-ligated stomachs were filled with mannitol, GFSM mixture and honey (1800 mOsmol/kg water) to test the effect of the hyperosmolar solutions on gastric fluid content and acid secretion. The rate of gastric emptying of the three test solutions (1800 mOsmol/kg) was measured by the phenol red method. RESULTS: Intragastric administration of mannitol, GFSM mixture or honey prevented the formation of mucosal lesions in an osmolality-dependent manner. Using the pylorus-ligated stomach model, the test solutions led to a net increase of luminal fluid volume without affecting acid content. Hyperosmolar solutions presented a delayed gastric emptying if compared to a nonnutrient solution made of carboxymethyl cellulose. CONCLUSIONS: The observed results suggest that hyperosmolar solutions can prevent the formation of hemorrhagic lesions by luminal dilution of the necrotising agent and acid, an effect which may be potentiated by a lowered gastric emptying rate.     

Effects of intraruminal loads of saline or water followed by voluntary drinking in the dehydrated lactating goat

In five goats water deprivation for 26 h increased plasma osmolality, total plasma protein concentration, and plasma vasopressin (AVP) concentration to higher levels during lactation compared to nonlactation. At the end of the dehydration period intraruminal loads of saline or water (corresponding to 50% of the body weight loss) were given to lactating goats. The saline load decreased the plasma protein concentration below control levels, while plasma osmolality, Na concentration and AVP did not change. After the water load the plasma protein concentration stayed elevated. Plasma osmolality, Na concentration and AVP fell, but remained significantly above control levels. Both plasma renin activity (PRA) and aldosterone (PA) concentration increased after water, but decreased after saline administration. Three hours after the fluid loads the goats were offered water to drink. AVP decreased at the sight of water. After drinking, plasma osmolality, Na and AVP continued to decrease in water loaded animals, and fell also in saline loaded goats. PRA remained elevated, and PA increased in water loaded goats, while these hormones still were depressed in saline loaded goats. Mean renal 'free water clearance' became positive after drinking in both groups. It is concluded that the water losses with the milk cause lactating goats to become dehydrated more rapidly than non-lactating goats during water deprivation. Lowering of the plasma osmolality and Na concentration are more important than restoration of the plasma volume in suppressing the high plasma AVP concentration in the dehydrated lactating goat. The water diuresis, which occurred after voluntary drinking, indicates that the goats had not been able to anticipate their water deficit accurately.(ABSTRACT TRUNCATED AT 250 WORDS)