Edge profile analysis of Joint European Torus (JET) Thomson scattering data: Quantifying the systematic error due to edge localised mode synchronisation.

The Joint European Torus (JET) high resolution Thomson scattering (HRTS) system measures radial electron temperature and density profiles. One of the key capabilities of this diagnostic is measuring the steep pressure gradient, termed the pedestal, at the edge of JET plasmas. The pedestal is susceptible to limiting instabilities, such as Edge Localised Modes (ELMs), characterised by a periodic collapse of the steep gradient region. A common method to extract the pedestal width, gradient, and height, used on numerous machines, is by performing a modified hyperbolic tangent (mtanh) fit to overlaid profiles selected from the same region of the ELM cycle. This process of overlaying profiles, termed ELM synchronisation, maximises the number of data points defining the pedestal region for a given phase of the ELM cycle. When fitting to HRTS profiles, it is necessary to incorporate the diagnostic radial instrument function, particularly important when considering the pedestal width. A deconvolved fit is determined by a forward convolution method requiring knowledge of only the instrument function and profiles. The systematic error due to the deconvolution technique incorporated into the JET pedestal fitting tool has been documented by Frassinetti et al. [Rev. Sci. Instrum. 83, 013506 (2012)]. This paper seeks to understand and quantify the systematic error introduced to the pedestal width due to ELM synchronisation. Synthetic profiles, generated with error bars and point-to-point variation characteristic of real HRTS profiles, are used to evaluate the deviation from the underlying pedestal width. We find on JET that the ELM synchronisation systematic error is negligible in comparison to the statistical error when assuming ten overlaid profiles (typical for a pre-ELM fit to HRTS profiles). This confirms that fitting a mtanh to ELM synchronised profiles is a robust and practical technique for extracting the pedestal structure.

Coherence imaging of scrape-off-layer and divertor impurity flows in the Mega Amp Spherical Tokamak (invited).

A new coherence imaging Doppler spectroscopy diagnostic has been deployed on the UK's Mega Amp Spherical Tokamak for scrape-off-layer and divertor impurity flow measurements. The system has successfully obtained 2D images of C III, C II, and He II line-of-sight flows, in both the lower divertor and main scrape-off-layer. Flow imaging has been obtained at frame rates up to 1 kHz, with flow resolution of around 1 km/s and spatial resolution better than 1 cm, over a 40° field of view. C III data have been tomographically inverted to obtain poloidal profiles of the parallel impurity flow in the divertor under various conditions. In this paper we present the details of the instrument design, operation, calibration, and data analysis as well as a selection of flow imaging results which demonstrate the diagnostic's capabilities.

Maternal vitamin D deficiency programmes adult renal renin gene expression and renal function.

Renin is essential for renal development and in adult kidneys vitamin D deficiency increases renin gene expression. We aimed to determine whether maternal vitamin D deficiency upregulates fetal renal renin expression, and if this is sustained. We also examined growth and the long-term renal effects in offspring on a normal diet. Female Sprague-Dawley rats in UVB-free housing were fed either vitamin D deficient chow (DEF) or normal chow from 4 weeks and mated with vitamin D replete males at 10 weeks. Fetuses were collected at E20 or dams littered and the pups were weaned onto normal chow. Kidney mRNA levels for renin, (pro)renin receptor [(P)RR], transforming growth factor ß 1 (TGF-ß1), and nephrin were determined in E20 fetuses and in male offspring at 38 weeks. Renal function was assessed at 33 weeks (24 h, metabolic cage) in both sexes. Renal mRNA expression was upregulated for renin in fetuses (P < 0.05) and was almost doubled in adult male offspring from DEF dams (P < 0.05). Adult males had reduced creatinine clearance, solute excretion and a suppressed urinary sodium-to-potassium ratio (P < 0.05). Female adult DEF offspring drank more and excreted more urine (P < 0.05) but creatinine clearance was not impaired. We conclude that maternal vitamin D depletion upregulates fetal renal renin gene expression and this persists into adulthood where, in males only, there is evidence of sodium retention and compromised renal function. Importantly these effects occurred despite the animals being on a normal diet from the time of weaning onwards.

A field programmable gate array unit for the diagnosis and control of neoclassical tearing modes on MAST.

A real-time system has been developed to trigger both the MAST Thomson scattering (TS) system and the plasma control system on the phase and amplitude of neoclassical tearing modes (NTMs), extending the capabilities of the original system. This triggering system determines the phase and amplitude of a given NTM using magnetic coils at different toroidal locations. Real-time processing of the raw magnetic data occurs on a low cost field programmable gate array (FPGA) based unit which permits triggering of the TS lasers on specific amplitudes and phases of NTM evolution. The MAST plasma control system can receive a separate trigger from the FPGA unit that initiates a vertical shift of the MAST magnetic axis. Such shifts have fully removed m∕n = 2∕1 NTMs instabilities on a number of MAST discharges.

Minimagnetospheres above the lunar surface and the formation of lunar swirls.

In this paper we present in situ satellite data, theory, and laboratory validation that show how small-scale collisionless shocks and minimagnetospheres can form on the electron inertial scale length. The resulting retardation and deflection of the solar wind ions could be responsible for the unusual "lunar swirl" patterns seen on the surface of the Moon.

A 130 point Nd:YAG Thomson scattering diagnostic on MAST.

A Thomson scattering diagnostic designed to measure both edge and core physics has been implemented on MAST. The system uses eight Nd:YAG lasers, each with a repetition rate of 30 Hz. The relative and absolute timing of the lasers may be set arbitrarily to produce fast bursts of measurements to suit the time evolution of the physics being studied. The scattered light is collected at F/6 by a 100 kg six element lens system with an aperture stop of 290 mm. The collected light is then transferred to 130 polychromators by 130 independent fiber bundles. The data acquisition and processing are based on a distributed computer system of dual core processors embedded in 26 chassis. Each chassis is standalone and performs data acquisition and processing for five polychromators. This system allows data to be available quickly after the MAST shot and has potential for real-time operations.

Maternal renal dysfunction in sheep is associated with salt insensitivity in female offspring.

To examine the programming effects of maternal renal dysfunction (created by subtotal nephrectomy in ewes prior to mating; STNx), renal and cardiovascular function were studied in 6-month-old male and female offspring of STNx and control pregnancies. After studies were conducted on a low salt diet (LSD) some female offspring underwent salt loading (0.17 M NaCl in the drinking water for 5-7 days; HSD). On LSD both male and female offspring of STNx had similar mean arterial pressures (MAP), heart rates, cardiac outputs and renal function to those measured in offspring of control ewes. In female STNx offspring on a HSD, plasma sodium levels increased and haematocrits fell, indicating volume expansion (P < 0.05). Plasma renin levels were not suppressed despite the increases in plasma sodium concentrations, but aldosterone levels were reduced. In control animals plasma renin levels fell (P < 0.05) but there was no change in plasma aldosterone concentrations. There was a positive relationship between GFR and MAP which was present only in female STNx offspring. In conclusion, in STNx offspring there was an impaired ability to regulate glomerular filtration independent of arterial pressure, renin release was insensitive to a high salt intake and control of aldosterone secretion was abnormal. This study provides evidence of abnormal programming of the renin-angiotensin system and glomerular function in offspring of pregnancies in which there is impaired maternal renal function.

Design of a new Nd:YAG Thomson scattering system for MAST.

A new infrared Thomson scattering system has been designed for the MAST tokamak. The system will measure at 120 spatial points with approximately 10 mm resolution across the plasma. Eight 30 Hz 1.6 J Nd:YAG lasers will be combined to produce a sampling rate of 240 Hz. The lasers will follow separate parallel beam paths to the MAST vessel. Scattered light will be collected at approximately f/6 over scattering angles ranging from 80 degrees to 120 degrees. The laser energy and lens size, relative to an existing 1.2 J f/12 system, greatly increases the number of scattered photons collected per unit length of laser beam. This is the third generation of this polychromator to be built and a number of modifications have been made to facilitate mass production and to improve performance. Detected scattered signals will be digitized at a rate of 1 GS/s by 8 bit analog to digital converters (ADCs.) Data may be read out from the ADCs between laser pulses to allow for real-time analysis.

Inactivation of polyketide synthase and related genes results in the loss of complex lipids in Mycobacterium tuberculosis H37Rv.

AIMS: Phthiocerol dimycocerosate (PDIM) waxes and other lipids are necessary for successful Mycobacterium tuberculosis infection, although the exact role of PDIM in host-pathogen interactions remains unclear. In this study, we investigated the contribution of tesA, drrB, pks6 and pks11 genes in complex lipid biosynthesis in M. tuberculosis. METHODS AND RESULTS: Four mutants were selected from M. tuberculosis H37Rv transposon mutant library. The transposon insertion sites were confirmed to be within the M. tuberculosis open reading frames for tesA (a probable thioesterase), drrB (predicted ABC transporter), pks11 (putative chalcone synthase) and pks6 (polyketide synthase). The first three of these transposon mutants were unable to generate PDIM and the fourth lacked novel polar lipids. CONCLUSIONS: Mycobacterium tuberculosis can be cultivated in vitro without the involvement of certain lipid synthesis genes, which may be necessary for in vivo pathogenicity. SIGNIFICANCE AND IMPACT OF THE STUDY: The use of transposon mutants is a new functional genomic approach for the eventual definition of the mycobacterial 'lipidome'.

The effects of asphyxia on renal function in fetal sheep at midgestation.

To determine whether damage to the fetal kidneys plays a role in the formation of hydrops fetalis following a severe asphyxial episode, six chronically catheterised fetal sheep, at 0.6 gestation (90 days; term 150 days), were subjected to 30 min of complete umbilical cord occlusion. During the occlusion period, mean arterial pressure, heart rate and renal blood flow decreased (P < 0.001). There were falls in arterial pH and PO2 and a rise in PCO2 (P < 0.001). Urine flow rate decreased (P < 0.005), as did the excretion rates of sodium and osmoles (P < 0.05). However, by 60 min after release of occlusion, urine flow rate was similar to control values. By the end of day 1, most renal variables returned to normal. At post-mortem, 72 h after occlusion, all asphyxiated fetuses showed gross signs of hydrops. Body weight was higher (P < 0.05) due to fluid accumulation in the peritoneal (P < 0.001) and pleural cavities (P < 0.05) as well as subcutaneously (P < 0.05). Amniotic/allantoic fluid volume was increased (P < 0.05). Kidney histology was normal except for clusters of apoptotic cells in some proximal tubules. In conclusion, this severe asphyxial episode caused surprisingly little damage to the kidney and the changes in renal function were very transient. Thus renal damage was not important in the development of hydrops. Possibly, the midgestation fetal kidney has a limited capacity to increase urinary salt and water excretion in response to increased fluid delivery across the placenta.

Effect of exercise on the rat mammary gland: implications for carcinogenesis.

Physical activity has been associated with decreased risk for developing breast cancer yet to date, the mechanism remains unknown. The purpose of this investigation was to evaluate the effects of moderate exercise training on the normal mammary gland in an attempt to identify alterations or differences that might be associated with tumour inhibition. A total of 170 female Sprague-Dawley rats were randomized to baseline (n=10), exercise (EX; n=80), or sham-exercise groups (SHAM; n=80). Treadmill training (20-25 m min-1, 15% grade, 30 min day-1, 5 days week-1) was started at 28 days of age (DOA). Animals were killed at 28, 42, 56, 70 and 84 DOA. Mammary glands were evaluated by histology and immunohistochemistry. Terminal end buds (TEB), structures susceptible to carcinogenesis, were counted. Sexual maturation, estradiol and progesterone, and organ and muscle weights were also evaluated. No differences in growth, sexual maturation, or steroid hormones were observed in response to training. No difference in the number of TEBs was observed at any timepoint between EX and SHAM. Proliferation was significantly increased at 56 DOA and tended to be increased at 42 and 70 DOA in the EX animals whereas cell death was significantly increased at 70 DOA and tended to be increased at 84 DOA in the EX animals. These data suggest no difference in the number of carcinogen-susceptible structures as a result of moderate exercise. The changes in cell proliferation and apoptosis with exercise training suggest altered cell turnover that will necessitate future study particularly with relevance to carcinogenesis.

The selfish brain and the barker hypothesis.

1. Brain sparing is a feature of intra-uterine growth retardation (IUGR). This implies that there is a redistribution of metabolic supply so that body growth slows to a greater extent than brain growth. 2. Intra-uterine growth retardation, as evidenced by a low birthweight for gestational age is a predisposing factor for hypertension, cardiovascular disease and diabetes mellitus in adult life. 3. In species like humans, nephrogenesis is complete before birth. In the rat, it is completed shortly after birth. In both species, it can be shown that either undernutrition or IUGR is associated with reduced nephron number. 4. It has been proposed that oligonephropathy results in hyperfiltration, which ultimately leads to glomerulosclerosis and hypertension. The renin-angiotensin system (RAS) is necessary for normal renal development and fetal renal function. In the rat, blockade of the RAS in the first weeks of life by pharmacological agents reduces glomerular number and has been shown to cause hypertension in adult life. Renal denervation reduces the activity of the fetal RAS and also causes abnormal development of the renin-secreting cells. 5. There is tonic renal sympathetic nerve activity in the late gestation fetal sheep. The level of renal sympathetic nerve activity (RSNA) is influenced by the fetal behavioural state. 6. However, interactions between the developing kidney and the developing sympathetic nervous system are poorly understood. On the one hand, renal innervation may be important in the provision of neurotrophic factors that stimulate the development of the RAS and kidney. On the other, high levels of RSNA associated with circulating catecholamines and vasopressin may cause vasoconstriction and limit nephrogenesis. This latter effect could be a predisposing factor to adult hypertension and cardiovascular disease.

Cloning and characterization of a gene cluster for cyclododecanone oxidation in Rhodococcus ruber SC1.

Biological oxidation of cyclic ketones normally results in formation of the corresponding dicarboxylic acids, which are further metabolized in the cell. Rhodococcus ruber strain SC1 was isolated from an industrial wastewater bioreactor that was able to utilize cyclododecanone as the sole carbon source. A reverse genetic approach was used to isolate a 10-kb gene cluster containing all genes required for oxidative conversion of cyclododecanone to 1,12-dodecanedioic acid (DDDA). The genes required for cyclododecanone oxidation were only marginally similar to the analogous genes for cyclohexanone oxidation. The biochemical function of the enzymes encoded on the 10-kb gene cluster, the flavin monooxygenase, the lactone hydrolase, the alcohol dehydrogenase, and the aldehyde dehydrogenase, was determined in Escherichia coli based on the ability to convert cyclododecanone. Recombinant E. coli strains grown in the presence of cyclododecanone accumulated lauryl lactone, 12-hydroxylauric acid, and/or DDDA depending on the genes cloned. The cyclododecanone monooxygenase is a type 1 Baeyer-Villiger flavin monooxygenase (FAD as cofactor) and exhibited substrate specificity towards long-chain cyclic ketones (C11 to C15), which is different from the specificity of cyclohexanone monooxygenase favoring short-chain cyclic compounds (C5 to C7).

Selective down-regulation of AT2 receptors in uterine arteries from pregnant ewes given 24-h intravenous infusions of angiotensin II.

Previously, we showed that uterine arteries from late gestation pregnant ewes infused intravenously with angiotensin II (Ang II) for 24 h, displayed heightened responsiveness to Ang II in vitro. Furthermore, we found that a small population of ewes with a "preeclampsia-like" disorder also displayed this. Therefore, we have investigated the density and affinity of Ang II receptor subtypes in the uterine arteries from these groups. Ang II receptor binding was measured using 125I [Sar1Ile8] Ang II. Proportions of AT1 and AT2 receptors were determined by inhibiting 125I [Sar1Ile8] Ang II with losartan (AT1 antagonist) or PD 123319 (AT2 antagonist). Uterine arteries from 24-h Ang II-infused ewes had a lower proportion of AT2 receptors (56.2+/-2.3%) than control (saline-infused) ewes (84.1+/-1.0%; P<0.05). The density of AT2 receptors was reduced (P<0.05) while the density of AT1 receptors was not different. Thus, 24-h infusions of Ang II selectively down-regulated AT2 receptors in the uterine artery, resulting in heightened Ang II reactivity. By contrast, the binding properties of Ang II receptor subtypes in uterine arteries from ewes with the "preeclampsia-like" disorder were not different from control ewes.

Chronic effect of insulin-like growth factor I on renin synthesis, secretion, and renal function in fetal sheep.

In the adult, insulin-like growth factor I (IGF-I) increases glomerular filtration rate (GFR) and renal blood flow (RBF) during both acute and chronic treatment. To study its effects on the developing kidney, chronically catheterized fetal sheep (120 +/- 1 days gestation) were infused intravenously for up to 10 days with 80 microgram/h IGF-I (n = 5) or vehicle (0.1% BSA in saline, n = 6). In contrast to previous acute studies in adult rats and humans, after 4 h of IGF-I fetal GFR and RBF were unchanged. Fractional sodium reabsorption increased (P < 0.05). However, by 4 days, GFR per kilogram had risen by 35 +/- 13% (P < 0.05), whereas RBF remained unchanged. Tubular growth and maturation may have occurred, as proximal tubular sodium reabsorption increased by ~35% (P < 0.005). Therefore, despite a marked increase in filtered sodium (~30%, P < 0.05), fractional sodium reabsorption did not change. Although the effects of IGF-I on renal function were delayed, plasma renin activity and concentration were both elevated after 4 h and remained high at 4 days (P < 0.05). Despite this, arterial pressure and heart rate did not change. Kidneys of IGF-I-infused fetuses weighed ~30% more (P = 0.05) and contained ~75% more renin than control fetuses (P < 0.005). Thus, in the fetus, the renal effects of long-term IGF-I infusion are very different from the adult, possibly because IGF-I stimulated kidney growth.

Insulin-like growth factor I alters renal function and stimulates renin secretion in late gestation fetal sheep.

While it is known that treatment with insulin-like growth factor I (IGF-I) stimulates growth of the fetal kidney, nothing is known about the short term or long term effects of IGF-I on fetal renal function. To investigate the acute effects of IGF-I on fetal renal function and on the activity of the fetal renin-angiotensin system, studies were carried out in 12 chronically catheterized fetal sheep aged 120 +/- 1 days, before and during a 4 h I.V. infusion of IGF-I at 80 ug h-1. Seven control fetuses were infused over the same period with vehicle (0.1% bovine serum albumin in 0.15 M saline). IGF-I infusion increased plasma IGF-I concentrations by about 80%. There was a small fall in arterial PO2 (P < 0.01), arterial PCO2 increased (P < 0.05), plasma lactate levels increased (P < 0.01) and arterial pH fell (P < 0.05). Fractional bicarbonate reabsorption increased and bicarbonate excretion decreased (P < 0.05). Infusions of IGF-I had no sustained effect on fetal arterial pressure. Glomerular filtration rate (GFR) did not change significantly during IGF-I infusion, but renal blood flow (RBF) fell (P < 0.05). Therefore filtration fraction relative to control values increased (P < 0.05), suggesting that efferent arteriolar vasoconstriction had occurred. IGF-I infusion led to an antidiuresis (P < 0.01), a rise in urinary osmolality (P < 0.05) and a fall in free water clearance (P < 0.01). Since fetal PO2 fell, it is probable that these effects were mediated by arginine vasopressin. The excretion rates of sodium, chloride and phosphate were all reduced by 4 h of infusion (P < 0.05), because their fractional reabsorption rates were all increased (sodium, P < 0.01; chloride, P < 0.01; and phosphate, P < 0.05). Plasma renin concentration increased by 275 +/- 52% during infusion of IGF-I (P < 0.005). Plasma renin activity also increased (P < 0.005), while circulating angiotensinogen concentrations fell (P < 0.05). In the adult, IGF-I increases both RBF and GFR, enhances tubular reabsorption and stimulates the renin-angiotensin system. In the fetus, however, it decreased RBF and had no effect on GFR, but was associated with enhanced tubular function and intense stimulation of renin secretion. Some of these effects of IGF-I on fetal renal function may be involved in maturation of the kidney in preparation for life after birth.

The catechol estrogen, 4-hydroxyestrone, has tissue-specific estrogen actions.

Recent data indicate that the catechol estrogen, 2-hydroxyestrone (2-OHE(1)), has no effect on any target tissue including bone, whereas 16 alpha-hydroxyestrone (16 alpha-OHE(1)) exerts tissue-selective estrogen agonist activity. The effect of the catechol estrogen, 4-hydroxyestrone (4-OHE(1)), putatively associated with tumorigenesis, has not been studied in the skeleton. The purpose of this study was to assess the effect of 4-OHE(1) on tibia, uterine and mammary gland histology and blood cholesterol in ovariectomized (OVX'd) growing rats. Ten-week-old female Sprague-Dawley rats were injected subcutaneously with 200 microg/kg BW per day with 4-OHE(1), 17 beta-estradiol (E(2)) or vehicle for three weeks. OVX resulted in uterine atrophy, increased body weight, radial bone growth and cancellous bone turnover, and hypercholesterolemia. E(2) prevented these changes with the expected exception that the subcutaneous infusion of this high dose of estrogen did not prevent the hypercholesterolemia. 4-OHE(1) prevented the increase in blood cholesterol and the increase in body weight. 4-OHE(1) appeared to have partial estrogen activity in the uterus; uterine weight and epithelial cell height were significantly greater than the OVX rats but significantly less (twofold) than the E(2) animals. Analysis of variance indicated that 4-OHE(1) slightly decreased the periosteal mineral apposition rate (P<0.05) compared with vehicle-treated rats but had no effect on double-labeled perimeter or bone formation rate. Similarly, 4-OHE(1) was a partial estrogen agonist on cancellous bone turnover. The data suggest that the catechol estrogen, 4-OHE(1), unlike 2-OHE(1), has estrogen activity. Furthermore, the profile of activity differs from that of 16 alpha-OHE(1). Our results suggest that estrogen metabolites may selectively influence estrogen-target tissues and, concomitantly, modulate estrogen-associated disease risk.

Effect of cortisol on fetal ovine vascular angiotensin II receptors and contractility.

The renin angiotensin system is important in the regulation of fetal blood pressure. This study investigated the expression of angiotensin AT(1) and AT(2) receptors in the ovine fetal heart, aorta and umbilical artery, and how these receptors are affected by cortisol. Cortisol infusion into the fetus has previously been shown to cause an increase in fetal blood pressure. We hypothesised that this effect of cortisol is mediated by upregulation of the angiotensin AT(1) receptor. Binding studies performed on tissues with intact endothelium demonstrated both receptor subtypes in the fetal aorta and right ventricle, although the latter contained mainly angiotensin AT(2) receptors. In contrast, only angiotensin AT(1) receptors were found in the umbilical artery. Cortisol infusion into fetuses (3 mg/day for 3-5 days) caused a physiological increase in plasma cortisol levels to 29+/-4 nM. This was associated with an increase in systolic pressure (57.8+/-1.7 vs. 52.2+/-1.5 mm Hg, P<0.05), but cortisol had no effect on the density or affinity of angiotensin receptors, nor on the in vitro contractile responses of carotid and umbilical arterial rings to 5-microM angiotensin II. In conclusion, this study has demonstrated differential expression of angiotensin AT(1) and AT(2) receptors in the different regions of the ovine fetal cardiovascular system and that the angiotensin AT(1) receptor is functional. The lack of any effect of low doses of cortisol on these receptors and on the contractility of isolated fetal vessels to angiotensin II suggests cortisol acts by other mechanisms to raise fetal arterial pressure.

Renal acid-base and sodium handling in hypoxia and subsequent mild metabolic acidosis in foetal sheep.

1. To measure the renal contribution to acid-base homeostasis during hypoxia (not associated with hypercapnia) and in response to the subsequent mild metabolic acidosis and to determine the effects of this hypoxia on the renal handling of sodium, studies were performed in six chronically catheterized foetal sheep (129-138 days gestation) before, during and for 1 h after a 2 h period of hypoxia. 2. Hypoxia was induced in the conscious ewe by infusing nitrogen into the trachea. Foetal arterial oxygen tension fell to 12.0 +/- 0.6 mmHg (P < 0.001). Carbon dioxide tension fell during hypoxia (P < 0.001) and was still somewhat reduced in the recovery period (P < 0.005). Arterial pH fell progressively to 7.19 +/- 0.08 in the recovery period (P < 0.05). Plasma bicarbonate concentrations fell (P < 0.001) and lactate rose (P < 0.001). 3. Urinary pH and the excretion rates of bicarbonate, titratable acid, ammonium and net acid did not change during hypoxia. Ammonium excretion and, hence, generation of new bicarbonate increased in the recovery period (P < 0.05). 4. Renal sodium excretion progressively increased and was greatest after normoxia was restored (P < 0.05). This natriuresis was due to a fall in the reabsorption of sodium by the proximal tubule (P < 0.05). Proximal reabsorption of sodium was directly related to foetal pH (P < 0.0001) and bicarbonate reabsorption (P < 0.001). 5. It was concluded that: (i) the foetal kidneys began to contribute to the maintenance of acid-base balance within the first hour of recovery from a 2 h episode of hypocapnic hypoxia, even though the acidosis was relatively mild; and (ii) a reduction in bicarbonate reabsorption was probably the most important factor that limited sodium reabsorption by the renal tubule during this experiment.

Effects of bilateral nephrectomy and angiotensin II replacement on body fluids in foetal sheep.

1. To determine the importance of the kidneys in maintaining the normal volume and composition of foetal body fluids, measurements were made in 11 chronically catheterized foetuses (123-136 days) that had been bilaterally nephrectomized at least 5 days previously and compared with 10 intact foetuses (121-133 days). 2. The nephrectomized foetuses had reduced extracellular (ECV), blood, plasma and interstitial volumes per kg foetal weight (P < 0.005), reduced plasma chloride levels (P < 0.001) and were acidaemic, hypoxaemic and hypercapnaemic (P < 0.05) compared with intact foetuses. They also had reduced lung liquid production (P < 0.05) and reduced lung liquid sodium and osmolality levels (P < 0.05). Their arterial pressure was more variable between foetuses (P < 0.005) and was directly related to ECV/kg (P = 0.013). 3. To determine which of these changes were due to absence of the foetal renin-angiotensin system, seven chronically catheterized nephrectomized foetal sheep (124-132 days) were infused with replacement doses of angiotensin (Ang)II (1.5 micrograms/kg per h) for 3 days. Six nephrectomized foetuses were infused with 0.15 mol/L saline. 4. The AngII infusion was non-pressor. It prevented the fall in ECV that occurred in the control group (P < 0.05) and foetal plasma chloride concentration rose (P < 0.05). Blood gas status and lung liquid production rate did not change, but lung liquid sodium concentration fell (P < 0.05) and potassium concentration rose (P < 0.05). 5. Bolus injections of AngII (0.3-5 micrograms) were given to assess vascular sensitivity to AngII. This was not altered by either nephrectomy or AngII replacement. 6. It is concluded that the foetal kidneys are important for the maintenance of the normal volume and composition of foetal body fluids. Angiotensin II, perhaps because it promotes fluid transfer across the placenta, helps maintain foetal ECV and plasma chloride levels.