Biomedical subjects

Michel Baum

Publications and source records attributed to Michel Baum.

36 records · Page 2Linked to original sources

PubMed2004

Phosphatonin washout in Hyp mice proximal tubules: evidence for posttranscriptional regulation.

X-linked hypophosphatemia is the most common inherited form of rickets. It is characterized by renal phosphate wasting, leading to hypophosphatemia and an inappropriately normal or low serum level of 1,25(OH)2 vitamin D. Previous studies have pointed to a circulating factor or phosphatonin-inhibiting phosphate transport by decreasing mRNA of the proximal tubule NaP(i) cotransporter NaPi-2A. The present study examined the hypothesis that there was also posttranscriptional regulation of the NaPi-2A cotransporter in Hyp mice proximal tubules and whether the phosphate transport defect in Hyp mice persisted when they were studied in vitro. We found that the rate of phosphate transport in Hyp mice was <50% that in C57/B6 control mice. While phosphate transport remained stable during incubation with time in C57/B6 mice proximal tubules, it increased from 0.46 +/- 0.47 to 1.83 +/- 0.40 pmol x mm(-1) x min(-1) in Hyp proximal tubules (P < 0.01) consistent with phosphatonin washout in Hyp proximal tubules perfused in vitro. This time-dependent increase in phosphate transport was still observed in the presence of cycloheximide. There was also a reduction of proximal tubule apical NaPi-2A expression from Hyp mice compared with C57/B6 mice using single-tubule immunohistochemistry. Using immunohistochemistry, we demonstrate an increase in apical expression of the NaPi-2A transporter in proximal tubules perfused in vitro in Hyp mice even in the presence of bath cycloheximide. The increase in apical expression of the NaPi-2A transporter in proximal tubules perfused in vitro in Hyp mice was blocked by colchicine. These data are consistent with a rapidly reversible posttranscriptional defect in Hyp mice causing a reduction in phosphate transport.

Adsorption↗

PubMed2004

Maturation of the Na+/H+ antiporter (NHE3) in the proximal tubule of the hypothyroid adrenalectomized rat.

In previous studies examining the role of glucocorticoids and thyroid hormone on the maturation of the Na(+)/H(+) antiporter (NHE3), we found attenuation in the maturational increase in proximal tubule apical Na(+)/H(+) antiporter activity but no change in NHE3 mRNA abundance in either glucocorticoid-deficient or hypothyroid rats. In addition, prevention of the maturational increase in either hormone failed to totally prevent the maturational increase in Na(+)/H(+) antiporter activity. We hypothesized that one hormone played a compensatory role when the other was deficient. The present study examined whether combined deficiency of thyroid and glucocorticoid hormones would completely prevent the maturation of the Na(+)/H(+) antiporter. Adrenalectomy was performed in 9-day-old hypothyroid Sprague-Dawley rats, a time before the normal postnatal maturational increase in these hormones occurs. Nine- and 30-day-old adrenalectomized (ADX), hypothyroid rats had comparable NHE3 mRNA abundance, which was 5- to 10-fold less than 30-day-old ADX, hypothyroid rats that received corticosterone-thyroxine replacement and 30-day-old sham control rats (P < 0.05). Brush-border membrane NHE3 protein abundance was comparable in 9- and 30-day-old ADX, hypothyroid groups and approximately 20-fold lower than both the 30-day replacement and 30-day sham groups (P < 0.05). Similarly, the replacement and sham groups had higher sodium-dependent proton secretion than 9- and 30-day-old ADX, hypothyroid groups (P < 0.05). We conclude that combined deficiency of both hormones totally prevents the maturational increase in NHE3 mRNA and protein abundance and Na(+)/H(+) antiporter activity.

Adrenalectomy↗

PubMed2004

Neonatal acid base balance and disturbances.

Maintaining acid base balance presents a considerable challenge to the growing neonate. The infant must ingest protein for growth and development. The metabolism of sulfur containing amino acids leads to the production of protons that must be secreted by the kidney. In addition, the formation of hydroxyapatite for the mineralization of growing bone also leads to acid production. Thus, the growing infant must excrete approximately 2 to 3 mEq of acid per kilogram of body weight per day to avoid becoming acidotic. The mechanisms for excreting acid undergo complex maturational changes that predispose the neonate, and the premature neonate in particular, to a great risk for the development of acidosis. In addition, infants are susceptible to gastrointestinal disturbances that can lead to acidosis due to acute loss of bicarbonate in the stool. The kidney is then responsible for the production of new bicarbonate to restore the body's acid base balance. There are also a number of inherited disorders in the kidney that affect acid secretion and lead to acid base disturbances in neonates. This review discusses the mechanisms by which the kidney is capable of excreting acid as well as the developmental regulation of these processes and the basis of inherited disorders of acidification.

Acid-Base Equilibrium↗

PubMed2004

Ontogeny of renal sodium transport.

One of the main functions of the adult kidney is to maintain a constant extracellular fluid balance. The adult kidney does this, by and large, by filtering a massive quantity of fluid and reabsorbing the solutes needed to maintain volume and electrolyte homeostasis, while leaving the waste products to be excreted in the urine. One of the most precisely regulated functions of the adult kidney is to maintain sodium balance. The challenge of the neonatal kidney is even greater. It must maintain a positive salt balance for growth while the neonate is fed a diet that is very low in sodium. This review focuses on how the neonatal kidney reabsorbs NaCl with a special emphasis on the differences between the neonatal and adult kidney.

Biological Transport↗

PubMed2003

Antidiuretic hormone resistance in the neonatal cortical collecting tubule is mediated in part by elevated phosphodiesterase activity.

Neonates cannot concentrate their urine to the same degree as adults. One of the key factors in concentrating the urine is the renal collecting duct osmotic water permeability (Pf) response to antidiuretic hormone (ADH). Neonatal cortical collecting ducts have a blunted Pf response to ADH compared with adult tubules (Pf: 119.0 +/- 12.5 vs. 260.1 +/- 29.5 microm/s, P < 0.05). We found that the phosphodiesterase activity in the neonatal collecting ducts was higher than that in the adult collecting ducts (3,970 +/- 510 vs. 2,440 +/- 220 cpm.microg tubular protein-1.20 min-1, P < 0.05). After pretreatment of in vitro microperfused tubules with the nonspecific phosphodiesterase inhibitor IBMX (10-6 M in the bath), the Pf response to ADH in neonatal collecting ducts was 271.4 +/- 51.7 microm/s, which was identical to that of the adult collecting duct [315.3 +/- 31.3 microm/s, P = not significant (NS)]. Rolipram, a specific type IV phosphodiesterase inhibitor, lowered the elevated phosphodiesterase activity in the neonatal tubules to that in the adult tubules (2,460 +/- 210 vs. 2,160 +/- 230 cpm.microg tubular protein-1.20 min-1, P = NS). Neonatal tubules pretreated with rolipram (10-5 M) in the bath also had a Pf response to ADH that was comparable to that of the adult tubules (258.2 +/- 17.0 vs. 271.4 +/- 32.6 microm/s, P = NS). Thus the elevated phosphodiesterase activity in the neonatal tubules appears to be due to an increase in type IV phosphodiesterase activity. Hence, one of the key factors in the decreased ability of neonates to concentrate their urine is overactivity of phosphodiesterase in the cortical collecting duct that blunts the neonatal collecting duct Pf response to ADH.

1-Methyl-3-isobutylxanthine↗

PubMed2003

Thyroid hormone modulates rabbit proximal straight tubule paracellular permeability.

Proximal straight tubules (PST) from both neonatal and hypothyroid adult rabbits have a lower rate of passive volume absorption when perfused with a high-chloride solution simulating late proximal tubular fluid than adult rabbit PST. We hypothesized that the maturational increase in serum thyroid hormone levels mediates the developmental changes in PST paracellular permeability. Neonatal tubules had lower chloride permeability, higher transepithelial resistance, but comparable mannitol permeability compared with adult PST. The present in vitro microperfusion study directly examined whether thyroid hormone affects passive solute flux and whether thyroid hormone could explain the developmental changes in PST paracellular permeability. Passive chloride transport was 62.1 +/- 4.5, 23.1 +/- 7.7, and 111.6 +/- 5.6 pmol.mm(-1).min(-1) in PST from euthyroid, hypothyroid, and hypothyroid animals that received thyroid treatment, respectively (control different from hypothyroid and thyroid treatment at P < 0.05). This was due to a thyroid hormone-mediated change in chloride permeability (P(Cl)). Mannitol permeability was 3.65 + 1.03, -0.19 + 0.72, and 3.60 + 1.12 x 10(-6) cm/s in PST from euthyroid animals, hypothyroid animals, and hypothyroid rabbits that received thyroid replacement, respectively (P < 0.05 hypothyroid vs. euthyroid and thyroid replacement). We demonstrate that PST from hypothyroid animals have a higher passive P(Na)/P(Cl) and P(HCO3)/P(Cl) than euthyroid controls. Finally, we examined whether these changes in permeability were paralleled by a change in PST paracellular resistance. Resistance was measured by current injection and cable analysis. The resistance in PST from hypothyroid rabbits was 6.3 +/- 0.8 Omega.cm(2), which was not different from control of 4.8 +/- 0.7 Omega.cm(2), or 7.0 +/- 0.7 Omega.cm(2) in hypothyroid animals that received thyroid replacement. Therefore, the maturational increase in thyroid hormone levels does not fully explain the developmental changes in the paracellular pathway.

Animals↗

PubMed2003

Ontogeny of water transport in the rabbit proximal tubule.

Water transport across cell membranes is a fundamental biological problem. In the kidney, many nephron segments have mechanisms for transporting large quantities of water with minimal energy input. The proximal tubule reabsorbs two-thirds of the glomerular filtrate with a small transepithelial osmotic gradient as the driving force. In the adult proximal tubule, this is accomplished by the expression of aquaporin 1 (AQP1), the water channel located on the apical and basolateral membranes of the proximal tubule. The neonatal tubule has a much lower expression of AQP1, yet can still transport water with a small osmotic gradient. Thus, tubule properties other than AQP1 expression must allow for this to occur. There are two primary differences that account for this unexpectedly high osmotic water permeability of the neonatal proximal tubule. First, the lipid membrane of the neonatal tubule is more fluid than the adult tubule and therefore a larger fraction of the water can pass through the lipid bilayer. The second property is the fact that the neonatal tubule cells have a smaller cell volume, and thus, the intracellular compartment provides less resistance for the movement of water. This review will discuss postnatal maturation of proximal tubule water transport.

Aging↗

PubMed2003

Correction of proximal tubule phosphate transport defect in Hyp mice in vivo and in vitro with indomethacin.

X-linked hypophosphatemia is the most prevalent inherited form of rickets. In this disorder, rickets results from hyperphosphaturia and inappropriately normal levels of 1,25(OH)2-vitamin D. Current therapy with oral phosphate and vitamin D improves the rickets, but has significant morbidity and does not significantly affect the short stature and hypophosphatemia. In the present study, we demonstrate that Hyp mice, which have a mutation homologous to that in patients with X-linked hypophosphatemia, have a 2-fold greater urinary prostaglandin E2 (PGE2) excretion than C57/B6 mice. To determine whether PGs were involved in the pathogenesis of this disorder, Hyp and C57/B6 mice received i.p. injections with vehicle or indomethacin (1 mg/kg of body weight twice daily for 4 days) and were studied approximately 12 h after the last dose of indomethacin. In the Hyp mice, indomethacin treatment decreased the fractional excretion of phosphate from 13.0 +/- 3.2% to 2.2 +/- 1.1% (P < 0.05), and increased serum phosphate from 2.9 +/- 0.2 mg/dl to 4.1 +/- 0.2 mg/dl (P < 0.05). There was no effect of indomethacin in C57/B6 mice. Indomethacin did not affect serum creatinine or inulin clearance, demonstrating that the normalization of urinary phosphate excretion was not caused by changes in glomerular filtration rate. Indomethacin treatment increased renal brush border membrane vesicle NaPi-2 protein abundance in Hyp mice to levels comparable to that of C57/B6 mice, but had no effect in C57/B6 mice. In vitro isolated perfused proximal tubule studies demonstrate directly that 10-6 M bath indomethacin normalized the phosphate transport defect in Hyp mice but had no effect on C57/B6 mice. In conclusion, there is dysregulation of renal PG metabolism in Hyp mice, and indomethacin treatment normalizes the urinary excretion of phosphate by a direct tubular effect.

Animals↗

PubMed2003

Bone mineral density in children with myelomeningocele: effect of hydrochlorothiazide.

Children with myelomeningocele experience difficulty with ambulation, which leads to immobilization and secondary loss of bone mineral density (BMD). In addition, non-ambulatory myelomeningocele patients have higher urinary calcium losses than their ambulatory counterparts. Hydrochlorothiazide (HCTZ) is known to reduce urinary calcium loss and increase BMD in non-myelomeningocele patients with hypercalciuria. This study examines the effect of HCTZ on urinary calcium and BMD in non-ambulatory children with myelomeningocele. Thirteen of 20 non-ambulatory patients with myelomeningocele completed the year-long randomized double-blinded study (placebo = 7 and HCTZ = 6). Evaluation included electrolytes, PTH, osteocalcin, 1, 25-OH vitamin D, urinary pyridinolines/deoxypyridinolines (U(pyr/dpyr)), urinary calcium/creatinine (U(Ca/Cr)), and forearm BMD (dual X-ray absorptiometry). Follow-up electrolytes were obtained at 1-2, 6, and 12 months and U(Ca/Cr) and BMD was obtained again at 12 months. There were no initial differences between the placebo and HCTZ groups. U(Ca/Cr) decreased in the HCTZ group after treatment (0.20+/-0.09 vs. 0.04+/-0.02, p<0.05). However, forearm BMD ( z-scores) after 1 year remained unchanged in both the HCTZ (-5.95+/-0.98 to -5.86+/-0.92) and placebo (-7.19+/-0.69 to -6.67+/-0.63) groups. While use of HCTZ for 1 year did not affect BMD, it reduced urinary calcium excretion in non-ambulatory children with myelomeningocele.

Adolescent↗

PubMed2003

Association of hypocalcemia with a change in gentamicin administration in neonates.

Aminoglycosides are administered frequently to neonates with suspected sepsis. We report the association of hypocalcemia in term and near-term neonates receiving gentamicin therapy for >/=4 days after a change in dosing from every 12 h to every 24 h. The possible association with a higher gentamicin dose and longer dosing interval is described.

Anti-Bacterial Agents↗

PubMed2003

Hypothyroidism increases osmotic water permeability (Pf) in the developing renal brush border membrane.

The osmotic water permeability (Pf) of the rabbit proximal tubule brush border membrane vesicles (BBMV) increases during maturation and is mediated by an increase in aquaporin-1 (AQP1) protein expression. Serum thyroid hormone levels increase after birth and have been shown to play a role in the maturation of other renal transport functions. We examined the hypothesis that thyroid hormone plays a role in the maturational increase in osmotic water permeability. Hypothyroidism was induced by addition of 0.1% propylthiouracil (PTU) to the drinking water of pregnant rabbits (starting 9 d before delivery) and was continued until the rabbits were studied as adults (9-11 wk). Some animals received thyroid hormone replacement by daily injection with triiodothyronine (T3; 10 microg/100 g body weight) for three days before study. Pf was found to be higher in BBMV from hypothyroid (82.7 +/- 5.5 microm/s) than from euthyroid (60.6 +/- 4.0 microm/s) and T3-replacement rabbits (69.0 +/- 5.0 microm/s) (p < 0.05). The activation energy (Ea; in kcal/deg.mol) of Pf was not different among the three experimental groups (euthyroid 5.6 +/- 0.9, hypothyroid 4.9 +/- 0.8, T3-replacement 5.0 +/- 1.0; p = NS), nor was the percentage mercury inhibition of Pf (euthyroid 66.5 +/- 5.3, hypothyroid 74.2 +/- 3.2 and T3-replacement 73.1 +/- 4.3; p = NS). AQP1 expression, measured by immunoblotting, was highest in BBMV from hypothyroid rabbits (p < 0.05). Membrane fluidity, measured as steady-state generalized polarization (GP) of Laurdan, which is inversely related to membrane fluidity, was significantly different between the three groups (GP: euthyroid 0.307 +/- 0.004, hypothyroid 0.271 +/- 0.004 and T3-replacement 0.287 +/- 0.003; for all p < 0.05). These data demonstrate that the maturational increase in thyroid hormone levels is not responsible for the maturational increase in water transport. Surprisingly, congenital hypothyroidism in rabbits is associated with an increased Pf when rabbits are studied as adults. The higher Pf in hypothyroid adult rabbits is due to a higher expression of AQP1 protein as well as a greater membrane fluidity than in euthyroid rabbits.

Animals↗

PubMed2003

Dopamine acutely decreases apical membrane Na/H exchanger NHE3 protein in mouse renal proximal tubule.

BACKGROUND: Dopamine is a principal natriuretic hormone in mammalian Na+ homeostasis. Dopamine acutely alters glomerular filtration rate (GFR) and decreases Na+ absorption in both the proximal and distal nephron. Proximal tubule natriuresis is effected through inhibition of the apical membrane Na/H exchanger NHE3. METHODS: We examined whether dopamine directly and acutely decreases apical membrane NHE3 protein using renal tissue in two in vitro systems: renal cortical slices and in vitro perfused single tubules. After incubation with dopamine, NHE3 activity was measured by 22Na flux and NHE3 antigen was measured by immunoblot in apical membrane and total cellular membranes. RESULTS: Direct application of dopamine to either cortical slices or microperfused tubules acutely decreases NHE3 activity and antigen at the apical membrane of the proximal tubule. No change in total cellular NHE3 was detected. CONCLUSION: One mechanism by which dopamine causes natriuresis is via direct and acute reduction of NHE3 protein at the apical membrane via changes in NHE3 protein trafficking.

Animals↗

PubMed2003

Fetal origins of cardiovascular disease.

Several epidemiologic studies have shown that intrauterine growth retardation is a risk factor for the development of cardiovascular disease in later life. In this review, we discuss these epidemiologic studies and animal models that have been developed to investigate the pathophysiology of this phenomenon. We discuss data suggesting that intrauterine growth retardation leads to fetal exposure to maternal glucocorticoids. In addition, we present other data showing that fetal exposure of glucocorticoids during specific times of fetal development results in focal and segmental glomerulosclerosis, a reduced number of nephrons, hypertension, and diabetes. These studies suggest that at critical times during fetal development fetal injury programs the development of cardiovascular disease and diabetes in later life.

Animals↗

PubMed2003

Maturational changes in renal tubular transport.

PURPOSE OF REVIEW: This review examines the maturational changes that occur in renal tubules during postnatal development. RECENT FINDINGS: The ability to study transport in neonatal tubules and the use of molecular techniques have allowed studies that not only examine the mechanism of solute and water transport in neonates but also what causes the maturational changes in transport at a molecular and cellular level. SUMMARY: This review demonstrates that there are significant quantitative and qualitative differences in transport during postnatal maturation in every nephron segment. In some segments the maturational changes involve simply a change in abundance of transporters, while in others the difference in transport is due to changes in transporter isoforms, changes in paracellular permeability or changes in intracellular signaling that regulate the transporter. This review focuses on these changes and what is known about what causes the maturational changes in transport.

Biological Transport↗

PubMed2003

Prenatal dexamethasone programs hypertension and renal injury in the rat.

Dexamethasone is frequently administered to the developing fetus to accelerate pulmonary development. The purpose of the present study was to determine if prenatal dexamethasone programmed a progressive increase in blood pressure and renal injury in rats. Pregnant rats were given either vehicle or 2 daily intraperitoneal injections of dexamethasone (0.2 mg/kg body weight) on gestational days 11 and 12, 13 and 14, 15 and 16, 17 and 18, or 19 and 20. Offspring of rats administered dexamethasone on days 15 and 16 gestation had a 20% reduction in glomerular number compared with control at 6 to 9 months of age (22 527+/-509 versus 28 050+/-561, P<0.05), which was comparable to the percent reduction in glomeruli measured at 3 weeks of age. Six- to 9-month old rats receiving prenatal dexamethasone on days 17 and 18 of gestation had a 17% reduction in glomeruli (23 380+/-587) compared with control rats (P<0.05). Male rats that received prenatal dexamethasone on days 15 and 16, 17 and 18, and 13 and 14 of gestation had elevated blood pressures at 6 months of age; the latter group did not have a reduction in glomerular number. Adult rats given dexamethasone on days 15 and 16 of gestation had more glomeruli with glomerulosclerosis than control rats. This study shows that prenatal dexamethasone in rats results in a reduction in glomerular number, glomerulosclerosis, and hypertension when administered at specific points during gestation. Hypertension was observed in animals that had a reduction in glomeruli as well as in a group that did not have a reduction in glomerular number, suggesting that a reduction in glomerular number is not the sole cause for the development of hypertension.

Animals↗

PubMed2002

Developmental changes in rabbit proximal straight tubule paracellular permeability.

The early proximal tubule preferentially reabsorbs organic solutes and bicarbonate over chloride ions, resulting in a luminal fluid with a higher chloride concentration than that in blood. From this late proximal tubular fluid, one-half of NaCl reabsorption by the adult proximal tubule is active and transcellular and one-half is passive and paracellular. The purpose of the present in vitro microperfusion study was to determine the characteristics of passive chloride transport and permeability properties of the adult and neonatal proximal straight tubules (PST). In tubules perfused with a late proximal tubular fluid, net passive chloride flux was 131.7 +/- 37.7 pmol x mm(-1) x min(-1) in adult tubules and -17.1 +/- 23.3 pmol x mm(-1) x min(-1) in neonatal proximal tubules (P < 0.01). Chloride permeability was 10.94 +/- 5.21 x 10(-5) cm/s in adult proximal tubules and -1.26 +/- 1.84 x 10(-5) cm/s in neonatal proximal tubules (P < 0.05). Thus neonatal PST have a chloride permeability not different from zero and have no net passive chloride transport. Bicarbonate permeability is also less in neonates than adults in this segment (-0.07 +/- 0.03 x 10(-5) vs. 0.93 +/- 0.27 x 10(-5) cm/s, P < 0.01). Neonatal PST have higher sodium-to chloride and bicarbonate-to-chloride permeability ratios than adult PST. However, mannitol and sucrose permeabilities were not different in adult proximal tubules and neonatal PST. Transepithelial resistance was measured using current injection and cable analysis. The resistance was 6.7 +/- 0.7 Omega x cm(2) in adult tubules and 11.3 +/- 1.4 Omega x cm(2) in neonatal PST (P < 0.01). In conclusion, there are significant maturational changes in the characteristics of the PST paracellular pathway affecting transport in this nephron segment.

Animals↗

PubMed2002

Renal nerve stimulation augments effect of intraluminal angiotensin II on proximal tubule transport.

The proximal tubule synthesizes and secretes angiotensin II into the lumen, where it regulates transport. Renal denervation abolishes the effect of angiotensin II on proximal tubule transport. Using in vivo microperfusion, we examined whether renal nerve stimulation modulates the effect of angiotensin II on transport. The effect of angiotensin II was assessed by measuring the decrease in volume reabsorption with the addition of 10(-4) M luminal enalaprilat. Luminal enalaprilat did not alter volume reabsorption (2.80 +/- 0.18 vs. 2.34 +/- 0.14 nl x mm(-1) x min(-1)). However, with renal nerve stimulation, enalaprilat decreased volume reabsorption (3.45 +/- 0.22 vs. 1.67 +/- 0.20 nl x mm(-1) x min(-1), P < 0.0005). The absolute and percent decrements in volume reabsorption with luminal enalaprilat were higher with renal nerve stimulation than with native innervation (1.78 +/- 0.19 vs. 0.46 +/- 0.23 nl x mm(-1) x min(-1), P < 0.02, and 51.8 +/- 5.0 vs. 14.6 +/- 7.4%, P < 0.05, respectively). Renal nerve stimulation did not alter the glomerular filtration rate or renal blood flow. Renal nerve stimulation augments the stimulatory effect of intraluminal angiotensin II. The sympathetic renal nerves modulate the proximal tubule renin-angiotensin system and thereby regulate proximal tubule transport.

Angiotensin II↗

PubMed2002

Water transport in neonatal and adult rabbit proximal tubules.

We have recently demonstrated that although the osmotic water permeability (P(f)) of neonatal proximal tubules is higher than that of adult tubules, the P(f) of brush-border and basolateral membrane vesicles from neonatal rabbits is lower than that of adults. The present study examined developmental changes in the water transport characteristics of proximal convoluted tubules (PCTs) in neonatal (9-16 days old) and adult rabbits to determine whether the intracellular compartment or paracellular pathway is responsible for the maturational difference in transepithelial water transport. The permeability of n-butanol was higher in the neonatal PCT than the adult PCT at all temperatures examined, whereas the diffusional water permeability was identical. Increasing the osmotic gradient increased volume absorption in both the neonatal and the adult PCT to the same degree. The P(f) was not different between the neonatal and the adult PCT at any osmotic gradient studied. To assess solvent drag as a measure of the paracellular transport of water, the effect of the osmotic gradient on mannitol and chloride transport were measured. There was no change in chloride or mannitol transport with the increased osmotic gradient in either group, indicating that there was no detectable paracellular water movement. In addition, the mannitol permeability of the neonatal PCT was found to be lower than that of the adult PCT with the isotonic bath (8.97 +/- 4.01 vs. 40.49 +/- 13.89 microm/s, P < 0.05). Thus the intracellular compartment of the neonatal PCT has a lower resistance for water transport than the adult PCT and is responsible for the higher than expected P(f) in the neonatal PCT.

1-Butanol↗