Extracellular water and blood pressure in adults with growth hormone (GH) deficiency: a genotype-phenotype association study.

OBJECTIVES: Growth hormone deficiency (GHD) in adults is associated with decreased extracellular water volume (ECW). In response to GH replacement therapy (GHRT), ECW increases and blood pressure (BP) reduces or remains unchanged. Our primary aim was to study the association between polymorphisms in genes related to renal tubular function with ECW and BP before and 1 year after GHRT. The ECW measures using bioimpedance analysis (BIA) and bioimpedance spectroscopy (BIS) were validated against a reference method, the sodium bromide dilution method (Br(-)). DESIGN AND METHODS: Using a candidate gene approach, fifteen single-nucleotide polymorphisms (SNPs) in nine genes with known impact on renal tubular function (AGT, SCNN1A, SCNN1G, SLC12A1, SLC12A3, KCNJ1, STK39, WNK1 and CASR) were genotyped and analyzed for associations with ECW and BP at baseline and with their changes after 1 year of GHRT in 311 adult GHD patients. ECW was measured with the Br(-), BIA, and BIS. RESULTS: Both BIA and BIS measurements demonstrated similar ECW results as the reference method. At baseline, after adjustment for sex and BMI, SNP rs2291340 in the SLC12A1 gene was associated with ECW volume in GHD patients (p = 0.039). None of the SNPs influenced the ECW response to GHRT. One SNP in the SLC12A3 gene (rs11643718; p = 0.024) and three SNPs in the SCNN1G gene [rs5723 (p = 0.02), rs5729 (p = 0.016) and rs13331086 (p = 0.035)] were associated with the inter-individual differences in BP levels at baseline. A polymorphism in the calcium-sensing receptor (CASR) gene (rs1965357) was associated with changes in systolic BP after GHRT (p = 0.036). None of these associations remained statistically significant when corrected for multiple testing. CONCLUSION: The BIA and BIS are as accurate as Br(-) to measure ECW in GHD adults before and during GHRT. Our study provides the first evidence that individual polymorphisms may have clinically relevant effects on ECW and BP in GHD adults.

Laminin-γ1 chain and stress inducible protein 1 synergistically mediate PrPC-dependent axonal growth via Ca2+ mobilization in dorsal root ganglia neurons.

Prion protein (PrP(C)) is a cell surface glycoprotein that is abundantly expressed in nervous system. The elucidation of the PrP(C) interactome network and its significance on neural physiology is crucial to understanding neurodegenerative events associated with prion and Alzheimer's diseases. PrP(C) co-opts stress inducible protein 1/alpha7 nicotinic acetylcholine receptor (STI1/α7nAChR) or laminin/Type I metabotropic glutamate receptors (mGluR1/5) to modulate hippocampal neuronal survival and differentiation. However, potential cross-talk between these protein complexes and their role in peripheral neurons has never been addressed. To explore this issue, we investigated PrP(C)-mediated axonogenesis in peripheral neurons in response to STI1 and laminin-γ1 chain-derived peptide (Ln-γ1). STI1 and Ln-γ1 promoted robust axonogenesis in wild-type neurons, whereas no effect was observed in neurons from PrP(C) -null mice. PrP(C) binding to Ln-γ1 or STI1 led to an increase in intracellular Ca(2+) levels via distinct mechanisms: STI1 promoted extracellular Ca(2+) influx, and Ln-γ1 released calcium from intracellular stores. Both effects depend on phospholipase C activation, which is modulated by mGluR1/5 for Ln-γ1, but depends on, C-type transient receptor potential (TRPC) channels rather than α7nAChR for STI1. Treatment of neurons with suboptimal concentrations of both ligands led to synergistic actions on PrP(C)-mediated calcium response and axonogenesis. This effect was likely mediated by simultaneous binding of the two ligands to PrP(C). These results suggest a role for PrP(C) as an organizer of diverse multiprotein complexes, triggering specific signaling pathways and promoting axonogenesis in the peripheral nervous system.

Cannabinoid CB1 receptor mediates glucocorticoid effects on hormone secretion induced by volume and osmotic changes.

The present study provides the first in vivo evidence that the cannabinoid CB(1) receptor mediates the effects of dexamethasone on hormone release induced by changes in circulating volume and osmolality. Male adult rats were administered with the CB(1) receptor antagonist rimonabant (10 mg/Kg, p.o.), followed or not in 1 hour by dexamethasone (1 mg/Kg, i.p.). Extracellular volume expansion (EVE, 2 mL/100 g of body weight, i.v.) was performed 2 hours after dexamethasone or vehicle treatment using either isotonic (I-EVE, 0.15 mol/L) or hypertonic (H-EVE, 0.30 mol/L) NaCl solution. Five minutes after EVE, animals were decapitated and trunk blood was collected for all plasma measurements. Rimonabant potentiated oxytocin (OT) secretion induced by H-EVE and completely reversed the inhibitory effects of dexamethasone in response to the same stimulus. These data suggest that glucocorticoid modulation of OT release is mediated by the CB(1) receptor. Although dexamethasone did not affect vasopressin (AVP) secretion induced by H-EVE, the administration of rimonabant potentiated AVP release in response to the same stimulus, supporting the hypothesis that the CB(1) receptor regulates AVP secretion independently of glucocorticoid-mediated signalling. Dexamethasone alone did not affect atrial natriuretic peptide (ANP) release stimulated by I-EVE or H-EVE. However, pretreatment with rimonabant potentiated ANP secretion induced by H-EVE, suggesting a possible role for the CB(1) receptor in the control of peripheral factors that modulate cardiovascular function. Rimonabant also reversed the inhibitory effects of dexamethasone on H-EVE-induced corticosterone secretion, reinforcing the hypothesis that the CB(1) receptor may be involved in the negative feedback exerted by glucocorticoids on the activity of the hypothalamic-pituitary-adrenal axis. Collectively, the results of the present study indicate that the CB(1) receptor modulates neurohypophyseal hormone secretion and systemic factors, such as corticosterone and ANP, thus participating in homeostatic responses to altered extracellular volume and plasma tonicity.

Extracellular ATP induces fast and transient non-selective cationic currents and cytosolic Ca2+ changes in human umbilical artery smooth muscle cells.

Ionotropic purinergic receptors (P2X) are expressed in endothelial and smooth muscle cells of blood vessels. ATP acting on smooth muscle P2X receptors is able to induce vasoconstriction in different kind of vessels. However, to our knowledge, there are no reports that directly show the activity of these purinergic receptors in native human vascular smooth muscle cells. In this work, we describe for the first time an ATP-induced current in freshly isolated human umbilical artery (HUA) smooth muscle cells. The current was measured by patch-clamp technique in whole-cell condition on cells clamped at -50 mV. At 100 µM of ATP the current showed a rapid activation and desensitization, and was carried by both Na(+) and Ca(2+). The current was completely blocked by suramin (300 µM) and partially blocked by 100 µM of Zn(2+) without affecting the kinetic of desensitization. All these properties suggest that the ATP-induced ionic currents are mediated through P2X(1)-like receptors. Moreover, we show that ATP transiently increased cytosolic Ca(2+) in "in situ" smooth muscle cells of intact HUA segments and that this response is dependent of extracellular and intracellular Ca(2+). These data expand the knowledge of purinergic receptors properties in vascular smooth muscle cells and the probable role of ATP as a paracrine modulator of contractile tone in a human artery which is fundamental for feto-placental blood flow.

Involvement of catecholaminergic medullary pathways in cardiovascular responses to acute changes in circulating volume.

Water deprivation and hypernatremia are major challenges for water and sodium homeostasis. Cellular integrity requires maintenance of water and sodium concentration within narrow limits. This regulation is obtained through engagement of multiple mechanisms and neural pathways that regulate the volume and composition of the extracellular fluid. The purpose of this short review is to summarize the literature on central neural mechanisms underlying cardiovascular, hormonal and autonomic responses to circulating volume changes, and some of the findings obtained in the last 12 years by our laboratory. We review data on neural pathways that start with afferents in the carotid body that project to medullary relays in the nucleus tractus solitarii and caudal ventrolateral medulla, which in turn project to the median preoptic nucleus in the forebrain. We also review data suggesting that noradrenergic A1 cells in the caudal ventrolateral medulla represent an essential link in neural pathways controlling extracellular fluid volume and renal sodium excretion. Finally, recent data from our laboratory suggest that these structures may also be involved in the beneficial effects of intravenous infusion of hypertonic saline on recovery from hemorrhagic shock.

Involvement of catecholaminergic medullary pathways in cardiovascular responses to acute changes in circulating volume

Water deprivation and hypernatremia are major challenges for water and sodium homeostasis. Cellular integrity requires maintenance of water and sodium concentration within narrow limits. This regulation is obtained through engagement of multiple mechanisms and neural pathways that regulate the volume and composition of the extracellular fluid. The purpose of this short review is to summarize the literature on central neural mechanisms underlying cardiovascular, hormonal and autonomic responses to circulating volume changes, and some of the findings obtained in the last 12 years by our laboratory. We review data on neural pathways that start with afferents in the carotid body that project to medullary relays in the nucleus tractus solitarii and caudal ventrolateral medulla, which in turn project to the median preoptic nucleus in the forebrain. We also review data suggesting that noradrenergic A1 cells in the caudal ventrolateral medulla represent an essential link in neural pathways controlling extracellular fluid volume and renal sodium excretion. Finally, recent data from our laboratory suggest that these structures may also be involved in the beneficial effects of intravenous infusion of hypertonic saline on recovery from hemorrhagic shock.

Hypothalamic cocaine- and amphetamine-regulated transcript and corticotrophin releasing factor neurons are stimulated by extracellular volume and osmotic changes.

Several studies suggest that hypothalamic cocaine- and amphetamine-regulated transcript (CART) may interact with the hypothalamic-pituitary-adrenal (HPA) axis in the control of neuroendocrine function and may also participate in cardiovascular regulation. Therefore, this study aimed to evaluate, in experimental models of isotonic (I-EVE) and hypertonic (H-EVE) extracellular volume expansion and water deprivation (WD), the activation of CART- and corticotrophin releasing factor (CRF)-immunoreactive neurons, as well as the relative expression of CART and CRF mRNAs in the paraventricular (PVN) and supraoptic (SON) nuclei of the hypothalamus. Both H-EVE (0.30M NaCl, 2mL/100g of body weight, in 1 minute) and 24 hours of WD significantly increased plasma sodium concentrations, producing, respectively, either an increase or a decrease in extracellular volume. I-EVE (0.15M NaCl, 2mL/100g of body weight, in 1 minute) evoked a significant increase in the circulating volume accompanied by unaltered plasma concentrations of sodium. CART-expressing neurons of both magnocellular and parvocellular hypothalamic divisions were activated to produce Fos in response to H-EVE but not in response to I-EVE. Furthermore, increased expression of CART mRNA was found in the PVN of H-EVE but not I-EVE rats. These data show for the first time that EVE not only activates hypothalamic CRF neurons but also increases CRF mRNA expression in the PVN. In contrast, WD increases the number of CART-immunoreactive neurons activated to produce Fos in the PVN and SON but does not change the number of neurons double labeled for Fos and CRF or expression of CRF mRNA in the PVN. These findings provided new insights into the participation of CART in diverse processes within the PVN and SON, including its possible involvement in activation of the HPA axis and cardiovascular regulation in response to changes in extracellular volume and osmolality.

Oestradiol potentiates hormone secretion and neuronal activation in response to hypertonic extracellular volume expansion in ovariectomised rats.

Secretion of vasopressin (VP), oxytocin (OT) and atrial natriuretic peptide (ANP) is an essential mechanism for the maintenance of hydromineral homeostasis. Secretion of these hormones is modulated by several circulating factors, including oestradiol. However, it remains unclear how oestradiol exerts this modulation. In the present study we investigated the participation of oestradiol in the secretion of VP, OT and ANP and in activation of vasopressinergic and oxytocinergic neurones of the supraoptic (SON) and paraventricular (PVN) nuclei of the hypothalamus in response to extracellular volume expansion (EVE). For this purpose, ovariectomised (OVX) rats treated for 7 days with vehicle (corn oil, 0.1 ml/rat, OVX+O group) or oestradiol (oestradiol cypionate, 10 µg/kg, OVX+E group) were subjected to either isotonic (0.15 m NaCl, 2 ml/100 g b.w., i.v.) or hypertonic (0.30 m NaCl, 2 ml/100 g b.w., i.v.) EVE. Blood samples were collected for plasma VP, OT and ANP determination. Another group of rats was subjected to cerebral perfusion, and brain sections were processed for c-Fos-VP and c-Fos-OT double-labelling immunohistochemistry. In OVX+O rats, we observed that both isotonic and hypertonic EVE increased plasma OT and ANP concentrations, although no changes were observed in VP secretion. Oestradiol replacement did not alter hormonal secretion in response to isotonic EVE, but it increased VP secretion and potentiated plasma OT and ANP concentrations in response to hypertonic EVE. Immunohistochemical data showed that, in the OVX+O group, hypertonic EVE increased the number of c-Fos-OT and c-Fos-VP double-labelled neurones in the PVN and SON. Oestradiol replacement did not alter neuronal activation in response to isotonic EVE, but it potentiated vasopressinergic and oxytocinergic neuronal activation in the medial magnocellular PVN (PaMM) and SON. Taken together, these results suggest that oestradiol increases the responsiveness of vasopressinergic and oxytocinergic magnocellular neurones in the PVN and SON in response to osmotic stimulation.

Would increased interstitial fluid flow through in situ mechanical stimulation enhance bone remodeling?

Bone accommodates to changes in its functional environment ensuring that sufficient skeletal mass is appropriately positioned to withstand the mechanical loads that result from functional activities. Increasing physical activity will result in increased bone mass, while the removal of functional loading would result in bone loss. Bone is a composite material made up of a collagen-hydroxyapatite matrix and a complex network of lacunae-canaliculi channels occupied by osteocyte and osteoblast processes, immersed in interstitial fluid. There are strong indications that changes in interstitial fluid flow velocity or pressure are the means by which an external load signal is communicated to the cell. In vitro studies indicate that shear stress, induced by interstitial fluid flow, is a potent bone cell behavior regulator. One of the forms of altering interstitial fluid flow is through the mechanical deformation of skeletal tissue in response to applied loads. Other methods include increased intramedullary pressure, negative-pressure tissue regeneration, or external mechanical stimulation. Analysis of these methods poses the question of process effectiveness. The efficacy of each method theoretically will depend on the mechanical efficiency of transmitting an external load and converting it into changes in interstitial fluid flow. In this paper, we combine recent knowledge on the effect of the bone's interstitial fluid flow, different fluid patterns, the role of gap junctions, and the concept of mechanical effectiveness of different methods that influence interstitial fluid flow within bone, and we hypothesize that the efficiency of bone remodeling can be improved if a small mechanical percussion device could be placed directly in contact with the bone, thus inducing local interstitial fluid flow variations. Enhancement of bone repair and remodeling through controlled interstitial fluid flow possesses many clinical applications. Further investigations and in vivo experiments are required. Practical methods and clinical apparatuses need to be conceived and developed to validate and facilitate the clinical use of this technique.

Do osmoregulators have lower capacity of muscle water regulation than osmoconformers? A study on decapod crustaceans.

Decapod crustaceans occupy various aquatic habitats. In freshwater they are osmoregulators, while marine species are typically osmoconformers. Freshwater crustaceans are derived from marine ancestors. The hypothesis tested here was that osmoregulators, which can rely on salt transport by interface epithelia to prevent extracellular disturbance, would have a lower capacity of tissue water regulation when compared with osmoconformers. Four species of decapod crustaceans (the marine osmoconformer crab Hepatus pudibundus, and three osmoregulators of different habitats) have been exposed in vivo to a salinity challenge, for up to 24 hr. Osmoregulators were: the estuarine shrimp Palaemon pandaliformis, the diadromous freshwater shrimp Macrobrachium acanthurus, and the hololimnetic red crab Dilocarcinus pagei. H. pudibundus displayed hemolymph dilution already after 0.5 hr in 25 per thousand, reaching approximately 30% reduction in osmolality, but its muscle degree of hydration did not increase. To make the different in vivo salinity challenges directly comparable, the ratio between the maximum change in muscle hydration with respect to the control value measured for the species and the maximum change in hemolymph osmolality was calculated (x 1,000): H. pudibundus (25 per thousand, 8.1% kg H(2)O/mOsm x 10(3))>P. pandaliformis (2 per thousand, 9.2)>M. acanthurus (30 per thousand, 12.6)>P. pandaliformis (35 per thousand, 16.7)>D. pagei (7 per thousand, 60.4). Muscle slices submitted in vitro to a 30% osmotic challenge confirmed in vivo results. Thus, the estuarine/freshwater osmoregulators displayed a lower capacity to hold muscle tissue water than the marine osmoconformer, despite undergoing narrower variations in hemolymph osmolality.

Muscle water control in crustaceans and fishes as a function of habitat, osmoregulatory capacity, and degree of euryhalinity.

This study aimed at detecting possible patterns in the relationship between Anisosmotic Extracellular Regulation (AER) and Isosmotic Intracellular Regulation (IIR) in crustaceans and teleost fish from different habitats and evolutionary histories in fresh water (FW), thus different osmoregulatory capabilities, and degrees of euryhalinity. Crustaceans used were the hololimnetic FW Aegla schmitti, and Macrobrachium potiuna, the diadromous FW Macrobrachium acanthurus, the estuarine Palaemon pandaliformis and the marine Hepatus pudibundus; fishes used were the FW Corydoras ehrhardti, Mimagoniates microlepis, and Geophagus brasiliensis, and the marine-estuarine Diapterus auratus. The capacity for IIR was assessed in vitro following wet weight changes of isolated muscle slices incubated in anisosmotic saline (~50% change). M. potiuna was the crustacean with the highest capacity for IIR; the euryhaline perciforms G. brasiliensis and D. auratus displayed total capacity for IIR. It is proposed that a high capacity for IIR is required for invading a new habitat, but that it is later lost after a long time of evolution in a stable habitat, such as in the FW anomuran crab A. schmitti, and the Ostariophysian fishes C. ehrhardti and M. microlepis. More recent FW invaders such as the palaemonid shrimps (M. potiuna and M. acanthurus) and the cichlid G. brasiliensis are euryhaline and still display a high capacity for IIR.

Congestive heart failure and renal complications.

Congestive heart failure is the leading cause of hospital admission among patients over the age of 65 years. It affects population within the United States, including Puerto Rico, presenting itself as the leading cause of heart related deaths worldwide. Its management can include pharmacologic agents which will affect neuroendocrine axis mainly but also include novel non-pharmacologic approaches such as ultrafiltration. The coexistence of heart failure and renal dysfunctions are very common within our medical community, especially within the western hemisphere, causing greater concerns amongst the medical field with increased research and investigation activity. This clinical review article will address the theme of congestive heart failure, highlighting the edema formation concept, volume homeostasis, cardio-renal syndrome and neuroendocrine pathways. The management of acute decompensated heart failure is discussed, primarily focusing with available novel non-pharmacologic approaches.

The extracellular matrix of the lung and its role in edema formation.

The extracellular matrix is composed of a three-dimensional fiber mesh filled with different macromolecules such as: collagen (mainly type I and III), elastin, glycosaminoglycans, and proteoglycans. In the lung, the extracellular matrix has several functions which provide: 1) mechanical tensile and compressive strength and elasticity, 2) low mechanical tissue compliance contributing to the maintenance of normal interstitial fluid dynamics, 3) low resistive pathway for an effective gas exchange, d) control of cell behavior by the binding of growth factors, chemokines, cytokines and the interaction with cell-surface receptors, and e) tissue repair and remodeling. Fragmentation and disorganization of extracellular matrix components comprises the protective role of the extracellular matrix, leading to interstitial and eventually severe lung edema. Thus, once conditions of increased microvascular filtration are established, matrix remodeling proceeds fairly rapidly due to the activation of proteases. Conversely, a massive matrix deposition of collagen fiber decreases interstitial compliance and therefore makes the tissue safety factor stronger. As a result, changes in lung extracellular matrix significantly affect edema formation and distribution in the lung.

The extracellular matrix of the lung and its role in edema formation

The extracellular matrix is composed of a three-dimensional fiber mesh filled with different macromolecules such as: collagen (mainly type I and III), elastin, glycosaminoglycans, and proteoglycans. In the lung, the extracellular matrix has several functions which provide: 1) mechanical tensile and compressive strength and elasticity, 2) low mechanical tissue compliance contributing to the maintenance of normal interstitial fluid dynamics, 3) low resistive pathway for an effective gas exchange, d) control of cell behavior by the binding of growth factors, chemokines, cytokines and the interaction with cell-surface receptors, and e) tissue repair and remodeling. Fragmentation and disorganization of extracellular matrix components comprises the protective role of the extracellular matrix, leading to interstitial and eventually severe lung edema. Thus, once conditions of increased microvascular filtration are established, matrix remodeling proceeds fairly rapidly due to the activation of proteases. Conversely, a massive matrix deposition of collagen fiber decreases interstitial compliance and therefore makes the tissue safety factor stronger. As a result, changes in lung extracellular matrix significantly affect edema formation and distribution in the lung.

A matriz extracelular é um aglomerado tridimensional demacromoléculas composta por: fibras colágenas (principalmente, tipos I e III), elastina, glicosaminoglicanos e proteoglicanos. No pulmão, a matriz extracelular tem várias funções, tais como: 1) promover estresse tensil e elasticidade tecidual, 2) contribuir para a manutenção da dinâmica de fluidos no interstício, 3) propiciar efetiva troca gasosa, 4) controlar a função celular através de sua ligação com fatores de crescimento, quimiocinas, citocinas e interação com receptores de superfície, e 5) remodelamento e reparo tecidual. A fragmentação e a desorganização da matriz extracelular pode acarretar edema intersticial e, eventualmente, edema alveolar grave. Logo, quando há aumento da filtração microvascular ocorre rápido remodelamento da matriz por ativação de proteases. Destarte, a deposição de fibras colágenas reduz a complacência intersticial limitando o edema. Em conclusão, modificações na matriz extracelular podem afetar a formação e distribuição do edema no pulmão.

Interaction of prolactin, ANPergic, oxytocinergic and adrenal systems in response to extracellular volume expansion in rats.

The present study evaluated the effect of acute extracellular volume expansion (EVE) induced by intravenous injection of isotonic (0.15 m NaCl) or hypertonic saline (0.3 m NaCl) on prolactin, corticosterone, vasopressin, oxytocin and atrial natriuretic peptide (ANP) secretion. Male Wistar rats were treated with bromocriptine, sulpiride or dexamethasone. After isotonic and hypertonic EVE, the control group showed a significant increase in the plasma concentrations of prolactin, corticosterone, ANP and oxytocin. The increase in ANP and oxytocin levels in response to hypertonic EVE was more pronounced than to isotonic EVE. Bromocriptine and sulpiride treatments did not modify corticosterone, ANP and oxytocin responses to either isotonic or hypertonic EVE. The increases in prolactin and oxytocin, but not ANP, were blocked in dexamethasone pretreated rats. In conclusion, isotonic or hypertonic EVE induced an increase in the plasma concentrations of prolactin, corticosterone, ANP and oxytocin. The increases in ANP and oxytocin were independent of plasma concentrations of prolactin. The increases in prolactin and oxytocin were blocked by the inhibition of the hypothalamo-pituitary-adrenal (HPA) axis by dexamethasone. However, dexamethasone did not alter the increase in ANP secretion induced by isotonic or hypertonic EVE. Therefore, prolactin might participate in regulation of the hydroelectrolytic balance in mammals; however, in the present study, there was no evidence for direct interaction with ANPergic and oxytocinergic systems. In addition, the responses of prolactin and oxytocin induced by isotonic or hypertonic EVE are modulated by the HPA axis.

Change in body water distribution index in infants who become stunted between 4 and 18 months of age.

OBJECTIVE: To evaluate body composition changes using bioelectrical impedance analysis and skinfold thickness measurements in infants from tropical areas who become stunted between 4-18 months of age. DESIGN AND MEASUREMENTS: Follow-up study. Extracellular water to total body water ratio index (length(2)/resistance at low to high frequency), peripheral fat (tricipital and subscapular skinfold thickness), and length-for-age index were studied at 4 and 18 months of age. SETTINGS: Low-income areas in four tropical regions (Congo, Senegal, Bolivia and New Caledonia). SUBJECTS: Infants were included in the analysis provided they were neither stunted nor wasted at 4 months. Two groups of infants were compared, those that were stunted at 18 months (n=61) or not (n=170). RESULTS: The extracellular water to total body water ratio index and the sum of skinfold thickness measurements were similar in the two groups at 4 months, and only the extracellular water to total body water ratio index was significantly different at 18 months. When no stunting appeared between 4 and 18 months, the change in the extracellular water to total body water ratio index was not linked with variations in length-for-age, and presented the expected pattern of variation in body water compartments. When stunting occurred, variation in length-for-age was related to significant changes in the extracellular water to total body water ratio index, the biggest increase in the proportion of extracellular water being found in the most stunted infants. Variations in the sum of the two skinfold thickness measurements presented the expected pattern for the 4-18 months growth and did not differ between the two groups. CONCLUSIONS: Multifrequency resistances suggested that stunting was associated with a lack of the expansion of the intracellular compartment that is expected during normal growth of cell mass, together with preserved fat mass. SPONSORSHIPS: Supported by grant 92L0623 from the French Ministry of Research, and by Institut de Recherche pour le Développement (IRD).