Effects of increased perfusion pressure on medullary collecting duct function

The role of the medullary collecting duct in pressure natriuresis has not been established. In vivo microcatheterization was used to study the effect of an acute increase in blood pressure induced by bilateral carotid artery and vagal nerve ligation on medullary collecting duct function in anaesthetized rats. Increased fluid and electrolyte excretion during pressure natriuresis were accompanied by increased delivery of water, sodium, chloride, and potassium to the beginning of the medullary collecting duct, a change that was significantly greater than in a second series of time-control animals. These increases in delivery were within the range for which constant fractional NaCl reabsorption had been found previously. However, during increased perfusion pressure, reabsorption of both sodium and chloride in the medullary collecting duct as a fraction of delivered load were reduced from 81 +/- 4.1 to 51 +/- 9.3% (p less than 0.01) and from 65.7 +/- 6.0 to 42.7 +/- 9.1% (p less than 0.01), respectively. No significant changes in medullary collecting reabsorption were seen in the time controls. We conclude that increased perfusion pressure, in addition to increasing delivery to the medullary collecting duct, also inhibits sodium chloride reabsorption in this nephron segment.     

Molecular mechanisms of ANP inhibition of renal sodium transport.

ANP, a hormone secreted by the atria of mammalian hearts in response to volume expansion, increases urinary sodium excretion in part by inhibiting sodium reabsorption across the inner medullary collecting duct. A number of nephron segments may contribute to the ANP-induced natriuresis; however, this review will focus on the cellular mechanisms of ANP inhibition of electrogenic sodium reabsorption by the inner medullary collecting duct. Patch-clamp studies conducted on rat inner medullary collecting duct cells in primary culture revealed that ANP, via its second messenger cGMP, inhibits electrogenic sodium reabsorption by reducing the open probability of a cation channel located in the apical membrane. Cyclic GMP inhibits the cation channel and thereby sodium reabsorption by two mechanisms. First, cGMP inhibits the channel by a phosphorylation-independent mechanism, by binding either to an allosteric modifier site on the channel or to a regulatory subunit. Second, cGMP inhibits the channel by activating cGMP-dependent protein kinase, which by a sequential pathway involving the GTP-binding protein, Gi, inhibits the channel. These cGMP-dependent mechanisms inhibiting sodium reabsorption across the inner medullary collecting duct account for a substantial component of the natriuresis following a rise in ANP levels.     

Interaction of amiloride and hydrochlorothiazide with atrial natriuretic factor in the medullary collecting duct

Medullary collecting duct function was studied using the in vivo microcatheterization technique in three groups of rats receiving amiloride, hydrochlorothiazide, or both diuretics. In each group of animals, atrial natriuretic factor (ANF99-126) was given in the second phase of the experiment. The combination of amiloride and hydrochlorothiazide resulted in a more marked natriuresis than either diuretic given as a single agent. Sodium reabsorption in the medullary collecting duct, as a fraction of the delivered load, was reduced from 64% (amiloride) and 69% (hydrochlorothiazide) to 29% (amiloride and hydrochlorothiazide). Atrial natriuretic factor reduced collecting duct sodium reabsorption when added to amiloride or hydrochlorothiazide to 23% and to 41%, respectively, but had no additional effect when given with amiloride and hydrochlorothiazide. Potassium excretion with amiloride and hydrochlorothiazide was intermediate between amiloride or hydrochlorothiazide given as single agents. With the diuretic combination, potassium transport showed no significant reabsorption or secretion along the medullary collecting duct, amiloride was associated with potassium reabsorption, and hydrochlorothiazide was associated with potassium secretion in the duct. The results confirm the importance of the medullary collecting duct as a site of diuretic action. The known additive effects of amiloride and hydrochlorothiazide on sodium excretion and the opposing effects of these agents on potassium excretion occur, to a major degree, in the medullary collecting duct. Furthermore, the additive effects of amiloride and ANF indicate that blocking of amiloride-sensitive sodium channels is not the only mechanism of action of ANF on duct salt transport in vivo.     

Collecting duct function in cis-platinum nephrotoxicity

Microcatheterization was used to study the effect of cis-platinum nephrotoxicity on inner medullary collecting duct function in anaesthetized rats. Osmolality of collecting duct fluid increased from the beginning to the end (papillary tip) of the collecting duct by only 69 +/- 11 mosmol/kg in cis-platinum treated rats (at 5-6 days) compared with 306 +/- 75 mosmol/kg in sham controls (p less than 0.01). Tubular fluid to plasma inulin concentration ratio was reduced at the beginning and end of the collecting duct. Tubular fluid sodium, chloride, and potassium concentrations were lower at the papillary tip in cis-platinum treated rats (p less than 0.01). The results indicate that collecting duct water reabsorption is reduced, but electrolyte reabsorption is normal (or even increased) in cis-platinum nephrotoxicity. Papillary tissue sodium chloride concentration was reduced in cis-platinum treated rats. We conclude that the characteristic decrease in urine concentrating ability in cis-platinum nephrotoxicity is not primarily the result of an intrinsic abnormality in collecting duct function but is secondary to decreased papillary hypertonicity resulting from impaired function in more proximal nephron segments, presumably the pars recta of the proximal tubule and the loop of Henle where previous studies have demonstrated abnormal function.     

Mechanisms of release and renal tubular action of atrial natriuretic factor

Inasmuch as atrial natriuretic factor (ANF) is apparently involved causally in the renal response to acute hypervolemia, it became of interest to study cellular mechanisms of release and renal tubular action. To study release mechanisms, freshly excised rat heart atria were incubated in vitro. Activation of the cellular adenylate cyclase system by either beta-adrenergic stimulation or the vasopressin analog deamino-8-D-arginine vasopressin did not result in ANF release. By contrast, activation of the polyphosphoinositide system by alpha-adrenergic stimulation or stimulation of the V1-type vasopressin receptors, and by a calcium ionophore or active phorbol ester, significantly increased natriuretic activity in the medium and reduced it in tissue. It is concluded, therefore, that activation of this latter system is the mechanism for ANF secretion from atrial myocytes. To test the effect of ANF on tubular transport in the medullary collecting duct, microcatheterization was used in rats before and during i.v. infusion of synthetic atrial peptide (23 amino acids). It was found that tubular delivery of salt to this part of the nephron was increased, and that reabsorption in the duct itself was reduced. In control experiments, increased delivery was associated with proportionately increased reabsorption, which demonstrated glomerulotubular balance in the nephron segment under normal conditions. The natriuretic effect of ANF, therefore, was not caused solely by enhanced tubular load, but included specific inhibition of duct sodium reabsorption as an essential feature of the renal response.     

Effect of saline infusion on kidney and collecting duct function in atrial natriuretic peptide (ANP) gene "knockout" mice.

Atrial natriuretic peptide (ANP) is thought to play a role in renal regulation of salt balance by reducing tubular reabsorption of sodium and chloride. Therefore, in the chronic absence of this hormone, a defect of salt excretion should be evident. We used an ANP gene deletion model to test this premise. F2 homozygous mutant mice (-/-) and their wild-type littermates (+/+) were fed an 8% NaCl diet prior to an acute infusion of isotonic saline. Arterial blood pressures, renal excretions of salt and water, as well as collecting duct transport of fluid and electrolytes were measured. Pressures were significantly higher in -/- compared with +/+ mice (139 +/- 4 vs. 101 +/- 2 mmHg; 1 mmHg = 133.3 Pa). There was no difference in glomerular filtration rate (-/- = 0.84 +/- 0.06; +/+ = 0.81 +/- 0.04 mL x min(-1) x g(-1) kidney weight). In the collecting duct, sodium and chloride reabsorptions were significantly higher in the -/- group than in the +/+ group. As a result, natriuresis and chloruresis were relatively reduced (U(Na)V: -/- = 8.6 +/- 1.1; +/+ = 14.0 +/- 1.1; U(Cl)V: -/- = 10.1 +/- 1.4; +/+ = 16.0 +/- 1.1 micromol x min(-1) x g(-1) kidney weight). We conclude that the absence of endogenous ANP activity in mice on a high-salt diet subjected to acute saline infusion causes inappropriately high reabsorption of sodium and chloride in the medullary collecting duct, resulting in a relative defect in renal excretory capacity for salt.     

The effect of isoproterenol on fluid and electrolyte transport in the inner medullary collecting duct

In the late distal and cortical collecting tubule, which is the principal regulatory site for potassium (K) excretion, vasopressin stimulates, and epinephrine via beta-adrenergic action, inhibits K secretion. In the inner medullary collecting duct (IMCD) we have shown that vasopressin also stimulates K secretion. The present experiments were designed to determine whether the beta-adrenergic agonist, isoproterenol, would induce K reabsorption in the IMCD, and (or) prevent a secretory response to acute KCl infusion. Two groups of rats, with or without isoproterenol administration (3 micrograms/h), were subjected to retrograde microcatheterization of the IMCD before and during infusion of 0.83 mol/h KCl. Isoproterenol reduced plasma K concentration and urinary K excretion, but the response to acute KCl infusion was qualitatively similar to control. Isoproterenol decreased delivery of potassium, chloride, and fluid to the IMCD, there was no net transport of K along the duct in either group, and KCl infusion did not result in K secretion in either group. The results indicate that isoproterenol may inhibit K secretion in the late distal or cortical collecting tubule. However, there was no statistically significant difference in K transport along the IMCD between isoproterenol and control groups. Reduced sodium excretion, which was found during isoproterenol administration both before and after KCl infusion, was associated with no change in sodium delivery but with increased sodium reabsorption in the IMCD. This increased sodium reabsorption may be a direct effect of isoproterenol, or may be due to reflex cardiovascular adjustments associated with systemic actions of the drug.     

Renal sodium transporter/channel expression and sodium excretion in P2Y2 receptor knockout mice fed a high-NaCl diet with/without aldosterone infusion

The P2Y(2) receptor (P2Y2-R) antagonizes sodium reabsorption in the kidney. Apart from its effect in distal nephron, hypothetically, P2Y(2)-R may modulate activity/abundances of sodium transporters/channel subunits along the nephron via antagonism of aldosterone or vasopressin or interaction with mediators such as nitric oxide (NO), and prostaglandin E(2) (PGE(2)) or oxidative stress (OS). To determine the extent of the regulatory role of P2Y(2)-R in renal sodium reabsorption, in study 1, we fed P2Y(2)-R knockout (KO; n = 5) and wild-type (WT; n = 5) mice a high (3.15%)-sodium diet (HSD) for 14 days. Western blotting revealed significantly higher protein abundances for cortical and medullary bumetanide-sensitive Na-K-2Cl cotransporter (NKCC2), medullary α-1-subunit of Na-K-ATPase, and medullary α-subunit of the epithelial sodium channel (ENaC) in KO vs. WT mice. Molecular analysis of urine showed increased excretion of nitrates plus nitrites (NOx), PGE(2), and 8-isoprostane in the KO, relative to WT mice, supporting a putative role for these molecules in determining alterations of proteins involved in sodium transport along the nephron. To determine whether genotype differences in response to aldosterone might have played a role in these differences due to HSD, in study 2 aldosterone levels were clamped (by osmotic minipump infusion). Clamping aldosterone (with HSD) led to significantly impaired natriuresis with elevated Na/H exchanger isoform 3 in the cortex, and NKCC2 in the medulla, and modest but significantly lower levels of NKCC2, and α- and β-ENaC in the cortex of KO vs. WT mice. This was associated with significantly reduced urinary NOx in the KO, although PGE(2) and 8-isoprostane remained significantly elevated vs. WT mice. Taken together, our results suggest that P2Y(2)-R is an important regulator of sodium transporters along the nephron. Pre- or postreceptor differences in the response to aldosterone, perhaps mediated via prostaglandins or changes in NOS activity or OS, likely play a role.     

Osmoregulation of natriuretic peptide receptor signaling in inner medullary collecting duct. A requirement for p38 MAPK.

In the inner medullary collecting duct of the terminal nephron, the type A natriuretic peptide receptor (NPR-A) plays a major role in determining urinary sodium content. This nephron segment, by virtue of its medullary location, is subject to very high levels of extracellular tonicity. We have examined the ability of medium tonicity to regulate the activity and expression of this receptor in cultured rat inner medullary collecting duct cells. We found that NaCl (75 mm) and sucrose (150 mm), but not urea (150 mm), increased natriuretic peptide receptor activity, gene expression, and promoter activity. The osmotic stimulus also activated extracellular signal-regulated kinase (ERK), c-Jun NH(2)-terminal kinase (JNK), and p38 mitogen-activated protein kinase (p38 MAPK). In the latter instance the beta isoform was selectively activated. Inhibition of p38 MAPK with SB203580 blocked the osmotic induction of receptor activity and expression, as well as receptor gene promoter activity, whereas inhibition of ERK with PD98059 had no effect. Cotransfection of p38 beta MAPK together with the receptor gene promoter resulted in amplification of the osmotic stimulation of the latter, whereas cotransfection of dominant negative MKK6, but not dominant-negative MEK, completely blocked the osmotic induction of receptor promoter activity. Collectively, the data indicate that extracellular osmolality stimulates receptor activity and receptor gene expression through a specific p38 beta-dependent mechanism, raising the possibility that changes in medullary tonicity could play an important role in the regulation of renal sodium handling in the terminal nephron.     

Renal blood flow, early distal sodium, and plasma renin concentrations during osmotic diuresis

Inconsistencies in previous reports regarding changes in early distal NaCl concentration (ED(NaCl)) and renin secretion during osmotic diuresis motivated our reinvestigation. After intravenous infusion of 10% mannitol, ED(NaCl) fell from 42.6 to 34.2 mM. Proximal tubular pressure increased by 12.6 mmHg. Urine flow increased 10-fold, and sodium excretion increased by 177%. Plasma renin concentration (PRC) increased by 58%. Renal blood flow and glomerular filtration rate decreased, however end-proximal flow remained unchanged. After a similar volume of hypotonic glucose (152 mM), ED(NaCl) increased by 3.6 mM, (P < 0.01) without changes in renal hemodynamics, urine flow, sodium excretion rate, or PRC. Infusion of 300 micromol NaCl in a smaller volume caused ED(NaCl) to increase by 6.4 mM without significant changes in PRC. Urine flow and sodium excretion increased significantly. There was a significant inverse relationship between superficial nephron ED(NaCl) and PRC. We conclude that ED(Na) decreases during osmotic diuresis, suggesting that the increase in PRC was mediated by the macula densa. The results suggest that the natriuresis during osmotic diuresis is a result of impaired sodium reabsorption in distal tubules and collecting ducts.     

The physiology of atrial natriuretic factor

Following the discovery of the natriuretic effect of atrial extract, our laboratory attempted to dissect the possible physiological role of atrial natriuretic factor. Initial micropuncture experiments demonstrated that the reduction of tubular sodium reabsorption was localized in the medullary collecting duct, a nephron site in which sodium transport was known to be inhibited after acute hypervolemia. Partial removal of the endogenous source of atrial natriuretic factor was associated with a reduced renal response to hypervolemia, confirming that the factor is causally involved in acute sodium balance. In vitro incubation of atrial tissue was used to investigate mechanisms of release of atrial natriuretic factor. It was found that agonists known to activate the intracellular polyphosphoinositide system in other tissues were effective in releasing natriuretic activity from the atria into the incubation medium. To determine whether atrial natriuretic factor might play a role in hypertension, atrial natriuretic content was measured in spontaneously hypertensive rats and their normotensive controls. Hypertension was associated with increased content. Since the renal response to exogenous factor was not impaired in these animals, we suggested that the increased content might play a compensatory role. Our early studies thus indicated that atrial natriuretic factor was a previously unrecognized hormone involved in cardiovascular regulation.     

Comparison of the natriuresis and chlorures is associated with glomerular hyperfiltration induced by atrial natriuretic factor or glucagon

The impact on renal sodium chloride reabsorption of an acute increase in glomerular filtration rate (GFR) induced by atrial natriuretic factor (ANF) or glucagon was examined in the conscious rat. These hormones have no direct effect on proximal solute transport and have opposite effects on distal transport. ANF and glucagon increased GFR to a comparable extent (2.0 ± 0.2 to 3.5 ± 0.4 ml/min, p<0.01, and 1.9 ± 0.1 to 3.3 ± 0.1 ml/min, p<0.001, respectively). While most (95–97%) of the increment in filtered sodium chloride was reabsorbed, a small portion (3–5%) escaped tubular reabsorption. Absolute sodium and chloride urinary excretion rates increased similarly in response to each hormone, by two- to three-fold. Slightly imperfect load-dependent sodium chloride reabsorptive response by the nephron, despite opposite direct effects on distal nephron transport, may account for the observed natriuresis and chloruresis associated with the acute glomerular hyperfiltration induced by ANF or glucagon administration.     

The effect of Ringer solution induced extracellular volume expansion on kidney function

The present study quantitated the effects of extracellular volume expansion on sodium and water excretion in 118 anesthetized dogs. The animals received a priming injection of 10 ml kg-1 Ringer solution i.v. which was followed by a constant Ringer solution infusion at a rate of 0.25 ml.min-1.kg-1 until the end of the experiment. Fifteen minutes after the start of the constant infusion the renal parameters were examined in 11 subsequent 15 min periods (the total time was 3 hours). Volume expansion produced no significant change in arterial blood pressure, glomerular filtration rate (GFR), plasma sodium and potassium concentration or, haematocrit, but did reduce the CPAH from 284 ml.min-1 to 218 ml.min-1 (the data were calculated for 100 gram wet kidney weight). There were constant significant increases in the urinary excretion rate from 0.84 ml.min-1 to 4.06 ml.min-1 and the 39% of the infused water was excreted during the experiment. Volume expansion also caused a significant increase in sodium excretion during the three first periods from 120 mumol.min-1 to 329 mumol.min-1 followed by a small but significant decrease. The sodium excretion at the end of the experiment was 221 mumol.min-1 and the 23% of the infused sodium was excreted in the course of the experiment. The increase of the water excretion during the volume expansion was associated with fall of the urine osmolality and the urine because hypoosmotic as compared to the plasma. We have provided evidence that vasopressin was not involved in the control of water excretion in our experiments. It is concluded that neither filtered sodium nor decreased aldosterone secretion can account for the increase in sodium excretion that occurs after Ringer solution loading in the dog. It has been proposed that a decrease in plasma protein concentration may decrease passive sodium reabsorption due to oncotic forces in the proximal tubule. The Ringer solution diuresis elicits a rise in medullary blood flow, thereby causing a washout of medullary sodium. This might dissipate the osmotic force for the back-diffusion of water from the collecting duct. Our studies indicate that the response of the diluting segments of the distal nephron to increased delivery of sodium depends upon the presence or absence of volume expansion. However the increase of the distal tubular loading activates the tubuloglomerular feedback which increases the proximal tubular reabsorption. Based on these assumptions our studies provide further evidence that the tubuloglomerular feedback regulates the blood pressure in the peritubular capillaries in the cortex around the proximal tubules.     

Effects of 7-day amino acid infusion on renal growth, function, and renin-angiotensin system in fetal sheep

These experiments examined whether renal growth and the fetal renin-angiotensin system could be stimulated by infusion of amino acids and whether chronic amino acid infusions restored glomerulotubular balance, which had been disrupted during 4-h infusions. Five fetal sheep aged 122 +/- 1 days gestation received an infusion of alanine, glycine, proline and serine in 0.15 M saline at 0.22 mmol/min for 7 days. Six control fetuses were given saline at the same rate (5 ml/h). Kidney wet weights after amino acid infusion were 28% larger than control fetuses (P < 0.05), and renal angiotensinogen mRNA levels were approximately 2.6-fold higher (P < 0.005). Circulating renin levels and renal renin mRNA levels were suppressed (P < 0.05), and renal renin protein levels tended to be lower. Arterial pressure was increased, and there was a marked, sustained natriuresis and diuresis. Glomerular filtration rate and filtered sodium were approximately two-fold higher throughout infusion (P < 0.05). Fractional proximal sodium reabsorption, suppressed at 4 h (from 73.4 +/- 6.5 to 53.7 +/- 10.2%), did not return to control levels (36.1 +/- 3.4% on day 7, P < 0.05). Distal sodium reabsorption was markedly increased (from 79 +/- 25 to 261 +/- 75 mumol/min by day 7, P < 0.005), but this was not sufficient to restore glomerulotubular balance. The resultant high rates of sodium excretion led to hyponatremia and polyhydramnios. In conclusion, long-term amino acid infusions increased renal angiotensinogen gene expression, kidney weight, and distal nephron sodium reabsorptive capacity but failed to restore proximal and total glomerulotubular balance.     

Natriuretic effect of atrial natriuretic peptide in diabetes insipidus rats

Washout of the solute concentration gradient in the renal medullary interstitium has been suggested to play a role in mediating the natriuretic response to atrial natriuretic peptide (ANP). The purpose of this study was to determine the effects of ANP 8-33 on sodium excretion in Brattleboro diabetes insipidus (DI) rats, in which medullary tonicity is known to be decreased as compared to Long-Evans (LE) control rats. Basal urine osmolality (Uosm) was significantly lower in DI rats as compared to LE rats (123 +/- 6 vs 673 +/- 38 mOsm/kg). Infusion of ANP 8-33 at a rate of 4 micrograms/kg/hr for 60 min resulted in a significantly greater increase in UnaV (delta 6.1 +/- 1.2 vs delta 2.9 +/- 0.7 microEq/min) and urine flow (delta 40 +/- 12 vs delta 8 +/- 7 microliter/min) in the LE rats than in the DI rats. The greater natriuresis occurred in the LE rats despite no significant change in Uosm. Fractional lithium reabsorption (an indicator of proximal sodium reabsorption) decreased similarly in both groups. Infusion of ANP had no effect on mean arterial pressure in LE and DI groups. In summary, infusion of ANP in the DI rat resulted in a significant natriuresis, albeit less than in LE rats. The natriuresis in the LE rats occurred despite no significant change in Uosm. These data suggest that mechanisms other than medullary washout are responsible for the natriuretic effects of ANP.     

A stop-flow study of intrarenal effects of atrial natriuretic factor

We performed paired series of stop-flow studies on six mongrel dogs to determine a possible nephron site of action of synthetic atrial natriuretic factor (ANF). The initial free-flow response to intrarenal infusion of 5 micrograms/min of synthetic ANF into mannitol-expanded dogs resulted in an increased urine flow rate (6.81 +/- 0.88 to 9.00 +/- 1.17 ml/min, P less than 0.05) and a 40% increase in sodium excretion (496 +/- 110 to 694 +/- 166 meq/min, P less than 0.025) when compared to paired control periods. Renal blood flow did not change, but the glomerular filtration rate increased 4% (47 +/- 5 to 49 +/- 6 ml/min, P less than 0.05). The filtered load of sodium increased 4% (P less than 0.05), and the fractional sodium excretion increased by 35% (P less than 0.01). Stop-flow experiments showed no difference in tubular sodium concentration or in the fractional sodium-to-inulin ratio at the nadir of sodium concentration, suggesting that no differences existed in distal tubular sodium handling. Further, no apparent differences were detected in collections representing the more proximal portions of the nephron. While we were able to demonstrate marked natriuresis in response to synthetic ANF, no tubular effect was discernible, and the natriuresis obtained appears to be predominantly a function of hemodynamic effects.     

Atrial natriuretic factor (ANF) increases urinary protein excretion in patients with essential hypertension: a possible role of ANF for renal handling of protein

Low dose iv infusion (0.01 and 0.03 micrograms/kg per min, for 30 min each) of alpha-human atrial natriuretic factor (alpha-hANF) produced a significant increase (+300%) in urinary protein excretion in patients with essential hypertension but not in normotensive controls, when their renal function was normal. The major component of excreted proteins induced by alpha-hANF infusion was presumed to be albumin on the basis of molecular weight (69,000) analyzed by sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis. Urine output and sodium and potassium excretion rates were increased dose-dependently by alpha-hANF infusion in the hypertensive patients in a similar fashion to those in the controls. Glomerular filtration rate (GFR) remained unchanged in the controls but was slightly increased in the patients (+33%) during the infusion. These results suggest that besides its previously recognized physiological functions such as natriuresis and diuresis, ANF plays an important role in the regulation of renal handling of proteins in patients with essential hypertension.     

The actions of cortisol on fetal renal function

Renal function was studied in 6 fetal sheep, aged 126-135 days, before and after 3 injection of 15 mg of cortisol given at intervals of 12 h. Cortisol caused a significant rise in both renal blood flow (P less than 0.05) and glomerular filtration rate (P less than 0.005), and in urine flow rate (P less than 0.02) but it did not consistently cause a natriuresis. The urinary pH was unchanged following cortisol treatment, but bicarbonate excretion increased. Urinary phosphate excretion was increased (P less than 0.005) because of a rise in filtered phosphate and a fall in phosphate reabsorption. The titratable acid excretion increased (P less than 0.005) but urinary ammonium excretion did not. The total amount of sodium reabsorbed increased after cortisol but the amount of sodium reabsorbed in the proximal tubule did not increase, so fractional reabsorption in the proximal tubule decreased from 61.7 +/- 4.1% to 47.3 +/- 4.2% (P = 0.01). The total amount of sodium reabsorbed in the distal tubule increased and distal fractional reabsorption increased from 33.3 +/- 2.4% to 47.3 +/- 4.2% (P less than 0.01). Cortisol may increase the capacity of the immature kidney to play a role in fluid and electrolyte homeostasis by increasing glomerular filtration rate and delivering more sodium and water to the distal nephron where the reabsorption of sodium and water can be modified independently and in accordance with need.     

Lack of anion effect on volume expansion natriuresis in the developing canine kidney

The renal response to volume expansion with sodium chloride or sodium bicarbonate was studied in 15 newborn and 13 adult dogs. Proximal and distal nephron function were estimated using the technique of distal nephron blockade. Fractional sodium reabsorption was 99.0 +/- 0.3% in newborn and 96.6 +/- 0.06% in adult during the NaCl expansion (P less than 0.01) and 98.1 +/- 0.7% in the newborn and 93.2 +/- 0.7% in the adult during NaHCO3 expansion (P less than 0.001). With either anion the higher fractional sodium reabsorption in the newborn was due to reabsorption of a greater fraction of the load presented to the distal nephron segment. The percent of the distal sodium load that was reabsorbed was 98.0 +/- 0.6% in the newborn and 92.2 +/- 1.0% in the adult during NaCl expansion, and 96.1 +/- 1.3% in the newborn and 81.5 +/- 2.4% in the adult during NaHCO3 expansion. Differences in distal nephron chloride, potassium and bicarbonate reabsorption among the groups support the hypothesis that the enhanced distal sodium reabsorption in the newborn occurred largely in the ascending loop of Henle with NaCl expansion, while it occurred in the late distal and cortical collecting tubules with NaHCO3 expansion. There was no difference between the natriuretic responses to NaCl or NaHCO3 in the newborn (P greater than 0.20); however, the natriuretic response to NaCl was less than that to NaHCO3 in the adult (P less than 0.001). This suggests that the bulk of the sodium that escaped reabsorption in Henle's loop during NaHCO3 expansion was reabsorbed in the late distal tubule in the newborn, but not in the adult.