Daily changes in foetal urine and relationships with amniotic and allantoic fluid and maternal plasma during the last two months of pregnancy in conscious, unstressed ewes with chronically implanted catheters

1. The fluid sacs and bladders of ten foetuses and the allantoic sacs of five foetuses were catheterized between 79 and 96 days gestational age and daily samples were withdrawn until lambs were born naturally at ~147 days. Maternal jugular plasma obtained daily allowed the nutritional status of each ewe to be regulated and monitored. All lambs were observed for 7 weeks, and at post-mortem no abnormalities were seen in those operated upon in utero.

2. The osmolality, [Na⁺], [K⁺], [Cl^-], [glucose], [fructose], [urea], [amino acid] and pH of all samples were measured.

3. Foetal surgery seemed to affect the actual concentrations of some solutes, but gestational trends in foetal fluid composition were unaltered.

4. Until about 7 days before birth the foetal urine osmolality, [Na⁺], [Cl^-] and [fructose] decreased, its [urea], [amino acid] and pH remained relatively constant, and from about 120 days gestational age the [K⁺] increased. During the last 7 days there was a marked increase in the osmolality and the concentrations of all these solutes, and a decrease in pH.

5. Entry of foetal urine into the fluid sacs tended to decrease the osmolality, [Na⁺], [K⁺], [Cl^-] and [glucose] of both foetal fluids and the [amino acid] of allantoic fluid, and tended to increase the [fructose] and [urea] of both fluids and the [amino acid] of amniotic fluid.

6. Changes in urine composition suggested large daily variations in the secretion of foetal antidiuretic hormone and also a rapid increase in its secretion during the last 7 days, and particularly the last 2-4 days before birth.

7. Changes in the [Na⁺]/[K⁺] ratios of foetal urine and allantoic fluid were parallel during post-operative recovery, during the course of pregnancy and immediately before birth, and this was consistent with a simultaneous action of foetal plasma corticosteroids on the foetal kidneys and chorioallantois.

8. Variations in the [fructose] of foetal urine and allantoic fluid were parallel to changes in their [Na⁺]/[K⁺] ratios and suggested an involvement of foetal corticosteroids in the regulation of the [fructose] of foetal plasma.

9. Further evidence has been presented supporting the hypothesis that maternal induced foetal hypoglycaemia effects a relative increase in the secretion of foetal corticosteroids having an action on the chorioallantois. Also, high concentrations of maternal plasma corticosteroids may decrease the permeability of the placenta to glucose.

     

Daily changes in amniotic and allantoic fluid during the last three months of pregnancy in conscious, unstressed ewes, with catheters in their foetal fluid sacs

1. Catheters were inserted into the maternal and foetal vasculatures of ten ewes, 100-139 days pregnant, and daily samples of uterine and umbilical blood and maternal jugular vein blood were taken for periods of 5-27 days after operation.

2. Catheters were inserted into the fluid sacs of nineteen foetuses, 60-97 days post-conception, and daily samples were withdrawn for up to 90 days from amniotic sacs (eleven foetuses) and for up to 70 days from allantoic sacs (eight foetuses). Maternal jugular plasma was obtained 3 times weekly and an approximation from its composition to that of uterine and umbilical plasma was made using results from the ewes and foetuses with vascular catheters.

3. The pH, osmolality, [Na⁺], [K⁺], [Cl^-], [urea] and [amino acid] of all samples were measured.

4. The nutritional status of all ewes was monitored throughout pregnancy. Most lambs were born naturally at ~ 147 days post-conception and their subsequent progress was observed.

5. Results at operation and from acute experiments were compared with those from conscious ewes and foetuses of the same gestational age to assess the nature and extent of the influence of the operative procedures on foetal fluid composition. The composition of amniotic fluid was influenced mainly by the anaesthetic and surgical procedures while that of allantoic fluid was affected largely by starvation of the ewe.

6. Changes during recovery from operation were followed and indicated that maternal and foetal plasma required about 3 days and the foetal fluids up to 7 days before stability of composition was achieved.

7. After recovery from operation, daily changes in the composition of each foetal fluid showed the same general pattern in all foetuses, but the absolute values of constituents sometimes showed large differences.

8. It is suggested that flow of foetal urine into the amniotic sac increased from 80 days gestational age, that urine flow into the allantoic sac decreased until about 100 days but did not cease thereafter, and that relative to foetal urine the influence of foetal pulmonary fluid on amniotic fluid composition was not great.

9. A relative impermeability of the amnion appeared to be a major factor influencing amniotic fluid composition, whereas pumping mechanisms in the chorioallantois seem to have been responsible largely for changes in the composition of allantoic fluid.

10. The quantity of solute relative to that of water within each sac appears to be a major determinant of changes in foetal fluid volumes.

11. Changes in the [Na⁺] and [K⁺] of allantoic fluid during the normal course of pregnancy were consistent with an increasing action of mineralo-corticoids on pumping mechanisms in the chorioallantois. Similar but more rapid changes seemed to be associated with acute and chronic episodes of maternal hypoglycaemia. Under these circumstances foetal hypoglycaemia may effect a relative increase in the secretion of foetal corticosteroids having an action on the chorioallantois.

12. The results from this study demonstrate clearly the value of using chronically catheterized animals, and it is suggested that their use in physiological studies on the conceptus must eventually supersede that of acute, anaesthetized preparations.

     

Effect of feeding on the diurnal rhythm of plasma cortisol and adrenocorticotrophic hormone concentrations in the pregnant ewe and sheep fetus.

The effects of two different feeding regimes on the 24 h profiles of maternal and fetal plasma cortisol and adrenocorticotrophic hormone (ACTH) concentrations were studied in eight pregnant ewes between 123 and 144 days of gestation. Once daily-fed ewes (n = 4) received 1 kg of lucerne-chaff at 11.00 h, and multi-fed ewes (n = 4) received 100-200 g of lucerne-chaff at 09.00, 11.00 and 13.00 h and then 150 g until 09.00 h the following day. There were significant differences between the two feeding groups in the 24 h profile of maternal plasma osmolality; once daily feeding at 11.00 h was associated with a peak in maternal plasma osmolality at 15.00 h whereas maternal plasma osmolality reached plateau levels at around 17.00 h in the multi-fed group. There were also differences between the two feeding groups in the 24 h profiles of maternal and fetal plasma glucose. Maternal and fetal plasma glucose reached peak concentrations at 19.00 h in the once daily-fed ewes in contrast to the multi-fed group, where a plateau in maternal and fetal plasma glucose was reached between 19.00 h and 09.00 h the following day. A significant diurnal variation in the plasma concentrations of cortisol was present in the once daily-fed ewes from 123 days gestation and in their fetuses after, but not before, 135 days gestation. Plasma cortisol peaked at 11.00 h in the ewes and at 13.00 h in the fetuses of this group. In the once daily-fed group there was also a significant diurnal variation in maternal and fetal plasma ACTH; plasma ACTH concentrations were highest at 11.00 h in the ewes aged between 123 and 144 days and in fetuses after 135 days gestation. In the multi-fed group, whilst ACTH was highest at 09.00 h in the ewes and at 13.00 h in the fetuses, there was no significant diurnal variation in the plasma concentrations of cortisol in the ewes or fetuses of this group at any stage between 123 and 144 days gestation.     

Daily changes in foetal and maternal blood of conscious pregnant ewes, with catheters in umbilical and uterine vessels

1. Blood gas tensions, pH, packed cell volume (PCV) and the levels of glucose, fructose and lactic acid have been followed in foetal and maternal blood for periods of 3-30 days in conscious ewes between 80 days gestation and term ( approximately 147 days).2. Blood samples were withdrawn through indwelling catheters placed in one or both umbilical vessels, a uterine vein and a maternal artery.3. The success of the operation appeared to depend on the maintenance of maternal blood gas and pH levels within normal limits as well as on the final position of the tip of the catheter. The difficulties and limitations of the technique are discussed.4. Foetal blood gas tensions, pH, PCV, lactic acid and glucose levels did not change markedly during the last 50-60 days of gestation. The fructose concentration fell during this period, the greatest change was between 100 and 120 days gestation.5. Small fluctuations in P(O2), P(CO2) and pH in umbilical venous blood were associated with similar changes in the uterine vein, so that the gradients across the placenta appeared to remain constant.6. Daily changes in maternal plasma glucose levels were reflected in similar changes in foetal plasma fructose and by much smaller alterations in the foetal glucose levels. The glucose concentration in the foetal plasma was less than 25% of that in maternal plasma.7. The existence of a general relationship between maternal plasma glucose and foetal plasma fructose was masked by the independent fall in fructose levels with age. However, at any given stage of gestation, there was a significant correlation between foetal fructose and maternal glucose.8. Few changes in the umbilical blood were associated with impending abortion or birth. Blood gas tensions remained constant, but a sharp fall in fructose levels often occurred 48 hr before any changes in pH, PCV and lactate concentration.9. Present and other findings on conscious animals are compared with previous observations on acute, anaesthetized preparations.     

The composition of foetal and maternal blood during parturition in the ewe

1. Changes in the composition of foetal and maternal blood have been followed during the last 5-10 days of gestation and throughout parturition in the conscious sheep.2. Catheters were placed in the foetal inferior vena cava through a tarsal vein and in a maternal uterine vein in ten ewes under sodium pentobarbitone anaesthesia. In four of the foetuses blood pressure and heart rates were recorded before and during parturition from an arterial catheter.3. Foetal blood gas tensions, pH and PCV remained stable during the latter part of gestation and throughout labour until 15 min before delivery, when P(O) (2) and pH fell while PCV and P(CO) (2) rose in about 50% of the foetuses examined.4. Metabolite levels were also relatively stable at the end of gestation. Plasma glucose in both maternal and foetal blood rose during the hour before birth, while foetal plasma lactate was elevated as early as 4 hr before birth and was unrelated to any maternal changes. Foetal fructose levels were maintained until after delivery.5. Rises in foetal blood pressure before birth were associated with uterine contractions. Foetal heart rate changes during labour varied in different individuals. The heart rate either fell gradually before birth or there was little change until a sudden drop at delivery.6. The most striking changes in the lamb occurred at, or a few minutes after, birth; pH and P(O) (2) fell, P(CO) (2) and PCV rose, and bradycardia at delivery was succeeded by prolonged tachycardia. There were marked increases in plasma glucose and lactic acid at this time.7. P(O) (2) rose rapidly once respiration was established, while pH and P(CO) (2) levels were restored within (1/2)-1 hr. Plasma FFA levels rose rapidly in the lambs 10-30 min after birth and remained high, while plasma glucose, lactate and fructose concentrations declined slowly in the 1-2 hr after birth, although suckling raised the plasma glucose levels. Considerable individual variation in the metabolite levels was found in both ewes and lambs.8. In the majority of ewes delivery was associated with an abrupt maternal hyperglycaemia, with a much smaller rise in lactate and virtually no change in maternal blood gases or pH.9. These findings are discussed in relation to existing information on new-born lambs and the human infant during birth.     

The development of some metabolic responses to hypoxia in the foetal sheep.

1. Foetal and maternal plasma metabolite and catecholamine concentrations have been measured in chronically catheterized sheep, 95-145 days pregnant. 2. With increasing gestational age there was rise in foetal plasma lactate, free fatty acid and ketone body concentration and in maternal plasma in free fatty acid and ketone body concentration. With the exception of alpha-amino nitrogen none of the plasma metabolites showed any correlation with foetal blood gas or pH values; alpha-amino N was inversely related to foetal blood pH. 3. Hypoxia in the foetuses was induced by causing the ewe to breathe 9% O2 with 3% CO2 in N2. This had a small effect on plasma metabolites in the ewe, mainly producing an increase in free fatty acid and ketone body concentration. 4. In the foetus hypoxia was associated with a large rise in plasma lactate and a small rise in alpha-amino N, the magnitudes of which did not change over the gestational range studied. Consistent and large increases in foetal plasma glucose, free fatty acid and ketone body concentration in response to hypoxia were seen only between 130 and 145 days. 5. In foetuses of 130-145 days the magnitude of the hypoxia-induced rise in plasma glucose and free fatty acid concentration was proportional to the plasma catecholamine concentration. 6. The concentration of acetate in foetal plasma was lower than and proportional to that in the maternal plasma. Neither concentration changed significantly during hypoxia. 7. The results are discussed in relation to the ability of the foetal sheep independently to control the concentration of its plasma metabolites and to mobilize its carbon stores at times of need. They indicate that in the sheep plasma catecholamines are important regulators of plasma glucose and free fatty acid concentrations late in foetal life.     

Sodium depletion of pregnant ewes and its effects on foetuses and foetal fluids

1. Some effects of sodium depletion were investigated in sheep at different stages of pregnancy ranging from 55 to 139 days. Sodium depletion was induced by draining the saliva from one parotid gland for a period of 6 days. Foetal samples were collected at the end of the depletion period.2. Sodium depletion of the ewe resulted in a fall in saliva Na(+) level and a rise in saliva K(+) level, a fall in plasma Na(+) and K(+) levels, a 35% reduction in plasma volume and a 16% reduction in body weight.3. In the Na(+) depleted ewes the sodium levels of the foetal plasma and amniotic fluid were lower and the volume of the allantoic fluid greater than those in the control ewes.4. It is concluded that sodium depletion of the ewe leads to a deficiency of sodium in the foetus.5. On the basis of these experiments and other reports it is postulated that a sodium deficient foetus, like a sodium deficient adult, responds to the deficiency by restricting sodium losses in the urine and by excreting water.     

Preloads of water, but not isotonic saline, reduce drinking in domestic fowls

Fowls were deprived of water for 2 or 6 hr, and then given graded intravenous (IV) injections of water or isotonic saline. With both levels of deprivation, water preloads caused dose-dependent reductions in water intake which matched closely the volumes of preload given, whereas isotonic saline preloads had no effect on drinking, and feeding was unaffected in both cases. These results imply that drinking elicited by short periods of water deprivation is a response to increased plasma osmolality rather than to a loss of extracellular fluid volume. In further experiments, water intakes were reduced by at least as much as the volume administered when undeprived fowls were given 6 hr continuous IV infusions or IV injections of water, and food intakes were also suppressed. Plasma analyses taken at the end of continuous infusions of water indicated a fall in osmolality during this time. It was concluded that whereas increases in plasma osmolality increase drinking in fowls, a fall in osmolality below normal inhibits both drinking and feeding. It is suggested that spontaneous drinking may be regulated mainly by changes in plasma osmolality, rather than in extracellular volume.     

Plasma catecholamines in foetal and adult sheep.

1. Foetal and maternal plasma catecholamine concentrations were measured during and after hypoxia (mean maternal Pa,02 44mmHg) in chronically catheterized sheep, 118-141 days pregnant. 2. In most foetuses the initial plasma catecholamines were smaller than 0.07 ng/ml. During hypoxia plasma adrenaline and noradrenaline always rose; there was a rise in arterial pressure and a fall in heart rate. 3. The initial catecholamine concentration in the ewes was smaller than 0.05-2.3 ng/ml. During hypoxia there was no consistent change; the maternal plasma concentrations were less than the foetal. 4. Infusion of adrenaline at 0.3 mug kg(-1) min(-1) to the ewe resulted in plasma catecholamine concentrations higher than those observed during hypoxia. There was a rise in heart rate but no consistent change in arterial pressure. 5. Infusion of adrenaline 0.4 mug kg(-1) min(-1) into the foetal jugular vein caused a rise in plasma concentration similar to that seen during hypoxia. There was a rise in heart rate but no significant change in arterial pressure. 6. The half-life of adrenaline and of noradrenaline in the maternal and foetal circulation was 0.25-1 min. There was no evidence of transfer of labelled catecholamine across the placenta.     

Influence of ruminal water-loading on renal sodium excretion and water intake following feeding in sheep.

We investigated the effect of ruminal water loading before feeding on the natriuretic and drinking responses that follow feeding. Six sheep fed 800 g of chaff drank 1360 +/- 150 mL during the 5 h immediately following feeding and increased renal Na excretion. Plasma Na concentration increased by 4 mmol L (-1) and plasma osmolality by 9 mosmol kg (-1) within 1.5 h and remained elevated. A rumen load of water administered before feeding prevented the increases in plasma Na and osmolality without affecting feeding. The natriuresis, water drinking and vasopressin secretion in response to feeding were abolished. Total sodium excreted during the experiment was halved in water-loaded animals compared with untreated animals (30.4 +/- 2.1 mmol (-1) cf. 63.8 +/- 2.9 mmol-1; P < 0.01). Ruminal loading with isotonic saline caused a 33% reduction in postprandial drinking, however, reducing cerebrospinal fluid NaCl concentration abolished postprandial drinking and natriuresis. Intravenous infusion of isotonic dextran appeared to delay the onset of water intake without changing the total volume of water drunk, suggesting a role of plasma volume in initiating drinking. We conclude from the data that central osmoregulatory mechanisms that include increased sodium excretion as well as thirst and vasopressin release are activated following food intake by sheep.     

Daily changes in the blood composition of conscious pigs with catheters in foetal and uterine vessels during late gestation

1. Catheters were inserted into the foetal carotid artery and maternal middle uterine artery and vein in twenty foetuses from fifteen sows, 91-105 days pregnant. Blood samples were collected from foetal and maternal circulations for periods of 7-21 days after surgery.2. Blood gas tensions, pH, packed cell volume (PCV) and the levels of glucose, fructose and lactic acid in conscious pigs were followed in foetal and maternal bloods during late pregnancy.3. Foetal blood gas tensions, pH, PCV, lactic acid and glucose levels did not change markedly during the last 20-25 days of gestation. Blood fructose concentration fell during this period with the greatest change occurring after 100 days gestation. Foetal and maternal blood pH values were higher than those reported in the sheep, cow, mare and rhesus monkey.4. Small changes in P(CO2) and pH in foetal carotid blood were associated with similar changes in maternal uterine venous blood, so that gradients between sow and foetus remained relatively constant.5. Daily changes in maternal blood glucose levels were associated with smaller changes in foetal blood glucose and fructose levels. Blood glucose concentrations in foetal blood were generally 40-70% of maternal concentrations. Over-all relationships between maternal blood glucose and foetal blood fructose concentrations were masked by the independent fall in foetal fructose levels with age.6. The present findings have been compared with previous observations on acute, anaesthetized preparations in pigs, and chronic preparations in other domestic animals.     

Interactions between maternal subtotal nephrectomy and salt: effects on renal function and the composition of plasma in the late gestation sheep fetus

Effects of altered maternal salt intake between 122 and 127 days gestation (term is 150 days) were studied in eight fetuses carried by ewes which had renal insufficiency caused by subtotal nephrectomy (STNxF) and seven fetuses carried by intact ewes (IntF). Plasma sodium and osmolality were increased in ewes with subtotal nephrectomy on a high-salt intake (0.17 m NaCl in place of drinking water for 5 days; P < 0.05). The STNxF had normal body weights. A high maternal salt intake did not affect fetal blood pressure or heart rate. Plasma osmolality was higher in STNxF (P < 0.001), and plasma sodium and osmolality were increased by high salt (P < 0.001 and P < 0.04, respectively). The STNxF had higher urinary osmolalities (P = 0.002), which were also increased by a high maternal salt intake (P = 0.03). Renal blood flow fell in STNxF in response to a high maternal salt intake, but increased in IntF (P = 0.003). In STNxF but not IntF, glomerular filtration rate and urinary protein excretion were positively related to fetal plasma renin levels (P < or = 0.01). It is concluded that the salt intake of pregnant ewes with renal insufficiency affects maternal and fetal osmolar balance, fetal plasma sodium and fetal renal function. Since STNxF also had altered renal haemodynamic responses to high maternal salt and evidence of renin-dependent glomerular filtration and protein excretion, we suggest that interactions between dietary salt and pre-existing maternal renal disease impair glomerular integrity and function in the fetus.     

The effects of pregnancy and maternal nutrition on the maternal renin-angiotensin system in sheep

Physiological changes occurring in the mother during pregnancy can determine the outcome of pregnancy in terms of birthweight and neonatal viability. Maternal adaptations include plasma volume expansion linked to enhanced activity of the renin-angiotensin system (RAS). The present study was designed to determine whether these changes occur very early in gestation, and the extent to which maternal nutrient restriction may compromise the maternal RAS. Using sheep, we have investigated the effects of pregnancy per se, maternal nutrient restriction and later restoration of maternal diet on maternal body weight, plasma volume and plasma renin concentration (PRC), and angiotensinogen (Aogen) and arginine vasopressin (AVP) concentration. During the period of placental growth (i.e. 28-80 days gestation) ewes were fed either a nutrient-restricted (NR) diet or were well fed (WF). NR ewes consumed between 3.2 and 3.8 MJ day(-1) of metabolisable energy (ME) which is close to 60 % of requirements taking into account the ME required for both ewe maintenance and growth of the conceptus in order to produce a 4.5 kg lamb at term. WF ewes consumed 150 % of ME requirements. Restoration of maternal diet between 80 and 140 days gestation (i.e. fed to satiety and consuming between 8 and 10.9 MJ day(-1), which is close to 150 % of ME requirements) followed previous nutrient restriction. Between pre-conception and 28 days gestation, plasma volume increased in conjunction with a decline in PRC and Aogen concentration. During the period of nutrient restriction ewe body weight did not increase and plasma volume was lower in NR than WF ewes. During this time there was no effect of maternal nutrition on PRC; however, Aogen concentration was lower in the NR group. From 80 days gestation following the rise in food intake for previously NR ewes, greater increases in ewe body weight, plasma volume and PRC occurred up to term compared with ewes that were well fed throughout gestation. Plasma AVP concentration was not significantly affected by either maternal nutrition or gestational age. In conclusion, the stimulus of moderately severe maternal nutrient restriction evoked smaller rises in maternal weight, plasma volume and Aogen concentration than occurred in ewes that were well fed throughout gestation. Following the restoration of maternal diet after 80 days gestation, PRC gradually rose to peak at term. These adaptations in the maternal RAS during the critical period of placental growth may have long-term effects on fetal development.     

Influence of ruminal water‐loading on renal sodium excretion and water intake following feeding in sheep

We investigated the effect of ruminal water loading before feeding on the natriuretic and drinking responses that follow feeding. Six sheep fed 800 g of chaff drank 1360 ± 150 mL during the 5 h immediately following feeding and increased renal Na excretion. Plasma Na concentration increased by 4 mmol L^–1 and plasma osmolality by 9 mosmol kg^–1 within 1.5 h and remained elevated. A rumen load of water administered before feeding prevented the increases in plasma Na and osmolality without affecting feeding. The natriuresis, water drinking and vasopressin secretion in response to feeding were abolished. Total sodium excreted during the experiment was halved in water‐loaded animals compared with untreated animals (30.4 ± 2.1 mmol^–1 cf. 63.8 ± 2.9 mmol^–1; P < 0.01). Ruminal loading with isotonic saline caused a 33% reduction in postprandial drinking, however, reducing cerebrospinal fluid NaCl concentration abolished postprandial drinking and natriuresis. Intravenous infusion of isotonic dextran appeared to delay the onset of water intake without changing the total volume of water drunk, suggesting a role of plasma volume in initiating drinking. We conclude from the data that central osmoregulatory mechanisms that include increased sodium excretion as well as thirst and vasopressin release are activated following food intake by sheep.     

Circadian variation of plasma atrial natriuretic peptide, cortisol and fluid balance in the goat

Circadian variation of plasma atrial natriuretic peptide (ANP), cortisol and fluid balance was studied in ten adult female goats. The concentrations of plasma antidiuretic hormone (ADH), electrolytes, creatinine and total protein, as well as plasma and urine osmolalities and renal electrolyte excretion and clearances (Cosm, CH2O, Ccrea), were used to evaluate fluid balance. At 3-h intervals, urine was collected from five goats and venous blood samples from all ten goats. Urethral catheterization had no effect on the results. Besides the lower plasma creatinine level in the dark than in daylight, no other changes were observed in relation to luminousness. Plasma concentrations of ANP, ADH, total protein and K, urine flow rate and osmolality, urine concentrations of Na, K and creatinine, renal Na and K excretion, Cosm, CH2O and Ccrea, and haematocrit showed no circadian variation. Circadian variation was observed in plasma osmolality (P < 0.05) and the concentrations of Na (P < 0.05) and creatinine (P < 0.05), with achrophases around 16:00 hours and nadirs between 01:00 and 07:00 hours. Changes in osmolality and Na followed the feeding schedule. There was a small elevation in plasma cortisol levels in six goats after midnight, which may be the consequence of circadian rhythm. In conclusion, the results suggest that in plasma ANP no circadian rhythm exists.     

Vasopressin and oxytocin excretion in the Brown-Norway rat in relation to aging, water metabolism and testosterone

There is considerable disagreement in the literature on changes in the hypothalamo-neurohypophyseal system (HNS) with aging: some reports support HNS degeneration, whereas others claim an activation of this system in senescence. In order to study age-related changes in vasopressin (VP) and oxytocin (OT) excretion in relation to water metabolism, six young (4 months) and 12 aged (34 months) male Brown-Norway rats were placed in metabolism cages. Since plasma testosterone levels have been reported to affect HNS activity and to decline progressively with age, half of the aged animals were given subcutaneous testosterone implants. Urine volume and water intake were significantly increased in aged animals, while urine osmolality was significantly reduced. These changes could not be attributed to diminished VP secretion, since 24-h urinary excretion of this peptide was elevated in the aged animals. In addition, 24-h OT excretion was elevated in the aged animals, indicating an overall activation of the HNS in senescence. VP excretion was significantly correlated with urine osmolality, urine volume and urinary VP concentration. No significant differences were observed between testosterone- and sham-implanted aged rats. It is concluded that the moderate polyuria/polydipsia in the senescent Brown-Norway rat is probably due to renal changes and is accompanied by a compensatory rise in both VP and OT secretion. Testosterone does not affect these changes.     

Influence of daily sodium intake on vasopressin secretion and drinking in dogs

Studies were carried out to determine the relationship between daily sodium intake, drinking, and vasopressin (AVP) secretion in normal conscious dogs. Chronic responses to 5-day elevations of daily sodium intake (200 meq/day) and 2-wk decreases in daily sodium intake (5 meq/day) were determined. Dogs were studied with ad libitum drinking and with water intake restricted to the amount drunk during the normal-sodium (30 meq/day) control period. Although acute elevations of plasma AVP occurred after a normal (40 meq Na) gastric load, chronic high-sodium intake resulted in no change of steady-state plasma AVP levels or daily AVP excretion (UAVP) with ad libitum drinking. Total water intake and frequency of drinking, however, increased nearly fourfold. In the absence of excess drinking, plasma AVP and UAVP both exhibited a nearly sixfold increase during the period of high-sodium intake. Despite elevations of plasma AVP, daily urine volume increased and urine osmolality rose only gradually during the 5 days of high-sodium intake. Chronic low-sodium intake also did not alter plasma AVP, but total water intake was reduced 20%. The data indicate that with water available, extracellular osmolality is controlled predominantly by drinking rather than by AVP secretion, that either osmolality or sodium concentration is the predominant controller of drinking and AVP secretion, and that daily water excretion need not be related directly to plasma AVP.     

Plasma vasopressin and cortical nephron function in aging rats.

The role of vasopressin and Henle's loop transport in age-related polyuria and decrease in urine osmolality was investigated in female WAG/Rij rats free of kidney disease. In these animals, urine osmolality dropped from 2000 mosmol/kg H2O to 1000-1200 mosmol/kg H2O between 10 and 30 months, and urinary volume increased in proportion. Vasopressin concentration measured in plasma withdrawn from conscious, unrestrained, chronically catheterized rats was not significantly different in 10, 20 and 30-month-old animals (mean values 2.5 +/- 0.7, 2.2 +/- 0.2 and 2.0 +/- 0.3 pg/ml (n = 8), respectively). This suggests an impaired responsiveness of old kidney to antidiuretic hormone. The possible involvement of Henle's loop in this defect was studied by micropuncture. Paired collections of tubular fluid were done in the early distal and late proximal convolutions of the same cortical nephrons. Single nephron filtration rates did not significantly differ with age. Tubular fluid osmolalities in the early distal convolution were 165 +/- 13, 178 +/- 9 and 160 +/- 11 (n = 14) mosmol/kg H2O in 10-, 20- and 30-month-old rats, indicating similar diluting capacity of the cortical thick ascending limb. The amount of sodium transported from lumen to peritubular space by Henle's loop was also unchanged with age as were water, calcium, magnesium and potassium reabsorptions. These data indicate that the age-related decrease in urine osmolality is not related to either a significant reduced vasopressin plasma concentration or an increased single glomerular filtration rate or a reduced transport capacity of Henle's loop of the cortical nephron. Rather they suggest an impaired response to vasopressin of other segments of the nephron that is, the medullary thick ascending limb of Henle's loop and/or the collecting duct.     

Periventricular preoptic-hypothalamus is vital for thirst and normal water economy

A midline stereotaxic lesion in rats destroying the periventricular tissue (lamina terminalis and preoptic-anterior hypothalamic periventricular stratum) surrounding the anteroventral third ventricle (AV3V) produces adipsia without other marked behavioral changes. Although food consumption is reduced in animals rendered adipsic by the lesion, feeding continued and intake is comparable to that of water-deprived-sham-lesioned animals. About half the rats recover drinking after a period of adipsia, but the others never resume water intake and become moribund. An analysis of urinary output indicates that adipsic animals fail to reduce urine volume and continue to elaborate an inappropriately dilute urine. The periventricular lesion-induced adipsia without compensating antidiuresis produces a significant rise in plasma protein, sodium, osmolality, and urea nitrogen which if untreated often results in acute encephalopathy leading to death. These data suggest that preoptic-anterior hypothalamic periventricular tissue houses vital neural elements which function in the modulation of water ingestive and conservation mechanisms directed at the maintenance of body fluid homeostasis.     

Distribution of ions and electrical potential differences between mother and foetus at different gestational ages in goats and sheep

1. Potential differences associated with the compartments of goat and sheep conceptuses have been measured in vivo and in vitro during the last half of gestation and the osmolarity, and the [Na(+)], [K(+)], and [Cl(-)] of maternal and foetal plasma and amniotic and allantoic fluid taken from these animals were determined.2. The potential difference (p.d.) patterns of both goats and sheep were the same.(a) The transplacental p.d. was about 71 mV (foetus negative) in the goat, and about 51 mV (foetus negative) in the sheep.(b) The amniotic fluid p.d. (i.e. the p.d. measured between the maternal extracellular fluid and the amniotic fluid) decreased as gestation advanced (from 110 to 70 mV in the goat, and 90 to 50 mV in the sheep) and was equal to the sum of the transplacental p.d. and a p.d. between the foetal blood and the amniotic fluid. The amniotic fluid was negative relative to both maternal and foetal blood.(c) An allantoic fluid p.d. (measured between the maternal extracellular fluid and the allantoic fluid) of about 107 mV in the goat, and about 96 mV in the sheep, was equal to the sum of the transplacental p.d. and a p.d. between the foetal blood and the allantoic fluid. The allantoic fluid was negative relative to both maternal and foetal blood.(d) The results suggest that p.d.s of the fluid sacs arise from activity between the foetal fluids and the blood perfusing the foetal membranes, and not from activity across the full thickness of the foetal membranes.3. The ionic concentrations were considered in relation to the electrochemical gradients found between the maternal and foetal fluid compartments to determine whether the ions were distributed according to electrochemical equilibrium.(a) It seems that ions in the amniotic fluid tend to equilibrate with foetal plasma, and not with maternal plasma or allantoic fluid, that changes in the [Na(+)] and [K(+)] of amniotic fluid can be accounted for largely in terms of passive factors, and that variations in the [Cl(-)] are associated with activity of an electrogenic Cl(-) pump directed from the foetal blood into the amniotic fluid.(b) It appears that ions in the allantoic fluid can exchange with those of both maternal and foetal plasma, that an electrogenic pump effects absorption of Na(+) from the allantoic fluid into the foetal blood, and that the [K(+)] and [Cl(-)] of allantoic fluid are maintained largely by passive exchange under the action of electrochemical gradients between maternal plasma and allantoic fluid, and between foetal plasma and allantoic fluid.4. The results considered in the context of Na(+) passage between mother and foetus call in question the general assumption that all Na(+) reaches the foetus by passing across the placenta.