Effects of renal lymphatic occlusion and venous constriction on renal function.

The effects of renal lymphatic occlusion or increased lymph flow due to renal vein constriction on renal function were investigated in rats. In each experiment, the renal lymphatics or vein of the left kidney were occluded or constricted and the right kidney served as a control. Occlusion of renal lymphatics caused renal enlargement, no change in glomerular filtration rate, a marked increase in urine flow and solute excretion without any change in urine osmolality, and enhanced urinary loss of urea, potassium, sodium and ammonium. Urea concentrations in medullary and papillary tissues were significantly elevated. Renal vein constriction caused renal enlargement and a marked drop in glomerular filtration rate, urine volume, urine osmolality and solute excretion. tissue concentrations of urea and potassium were decreased in the medulla and papilla and total tissue solute was significantly decreased in the papilla. The data indicate that in the rat, renal lymphatic occlusion traps urea in the medulla and induces a urea diuresis resulting in a large flow of normally concentrated urine. On the other hand, increased lymph flow secondary to renal vein constriction decreases medullary urea and potassium concentrations and papillary osmolality. These changes and the reduced glomerular filtration rate result in a small flow if dilute urine. Thus both renal lymphatic occlusion and enhanced lymph flow have a significant effect on renal function.     

Effects of long-term changes in medullary osmolality on heat shock proteins HSp25, hsp60, HSP72 and HSP73 in the rat kidney

 The influence of diuresis and antidiuresis on the expression of heat shock proteins (HSP) 25, 60, 72 and 73 in the renal cortex and outer and inner medulla of Wistar rats was analysed. Medullary osmolality was reduced by long-term diuresis (3% sucrose in the drinking water for 3 weeks) and subsequently enhanced by transition to a concentrating state by giving normal drinking water again in combination with deamino-D-arginine vasopressin (dDAVP) for 5 days. Western blot analyses revealed that neither HSP73 nor HSP60 was influenced by any treatment. The HSP72 level in the medulla was markedly reduced (50%) when osmolality was lowered and increased when tonicity was high. RNAse protection assays showed that the effects on HSP72 are parallelled in general by changes in HSP72 mRNA. While levels of HSP25 were not influenced, isoelectric focusing revealed that the degree of phosphorylation of outer and inner medullary HSP25 increased following both treatments. It thus seems that HSP73 and HSP60 are not directly involved in the long-term adaptation to varying medullary osmolalities. The correlation between changes in osmolality and amounts of the major stress-inducible HSP72 in the medulla implies that medullary hypertonicity is stressful for kidney cells. Furthermore, adaptation to pronounced changes in the osmolality of the environment most likely involves phosphorylation of HSP25. Received: 16 September 1997 / Received after revision and accepted: 9 December 1997     

Influence of prehydration on the changes in renal tissue composition induced by water diuresis in the rat

1. The composition of renal tissue was determined in rats before and immediately after intravenous infusion of dextrose (2.5 g/100 ml.) in amounts sufficient to administer a positive fluid load of 4% body weight over 2 hr. The rats were classified into three groups, according to the preinfusion urine osmolality: hydropaenia, normal and moderately diuretic (over 2400, 800-1500 and below 800 mu-osmoles/g H(2)O, respectively).2. In non-infused rats, the steepness of the corticomedullary osmolal gradient varied, due to differences in both water and solute (sodium and urea) contents, and was related to urinary osmolality. Whereas differences in medullary and papillary solute contents occurred between all three groups, papillary water content was significantly higher only in the moderately diuretic animals.3. Dextrose infusion caused the induction of water diuresis, the lowest urinary osmolalities being produced in the previously moderately diuretic animals.4. Dextrose infusion caused a considerable reduction in the steepness of the corticomedullary osmolal gradient in all rats, particularly in the previously hydropaenic animals, due to changes in both solute (sodium and urea) and water contents. Whereas reductions in medullary and papillary solute contents occurred in all three groups, there was no further increase in papillary water content from the already high values seen in the noninfused diuretic animals.5. Thus, dextrose infusion largely abolished any previous differences in tissue water content, whereas significant, though small, differences in osmolal (particularly urea) content persisted.6. These data are discussed in terms of changes and differences in endogenous antidiuretic hormone (A.D.H.) release.7. Changes in the magnitude and direction of the urinary-papillary urea concentration difference are discussed in terms of passive transport, with probable A.D.H.-induced changes in nephron urea permeability.     

Solute composition and heat shock proteins in rat renal medulla

 The high content of heat shock proteins (HSPs) 25 and 72 in the hyperosmotic inner medulla of the concentrating kidney has been ascribed to the high NaCl and urea concentrations in this kidney zone. To assess the effects of variations in the composition of solutes in the renal medulla on the intrarenal distribution of HSPs, rats were fed either a high- or low-Na diet for 3 weeks. These diets result in greatly differing urine and inner medullary solute composition. Sodium dodecyl sulphate polyacrylamide gel electrophoresis and Western blot techniques were used to analyse HSP25 and HSP72 in the cortex, outer medulla and inner medulla. In addition, the amounts of organic osmolytes (sorbitol, myo-inositol, betaine and glycerophosphorylcholine) and urea in the tissue were determined by high-performance liquid chromatography. Intra- and extracellular electrolyte concentrations at the papillary tip were measured by electron microprobe analysis. In the high-Na group, urine osmolality was about 1000 mosmol/kg lower than in rats fed a low-Na diet, due to lower urea concentrations. The sum of urine sodium and potassium concentrations, however, did not differ between the two groups. Neither in the outer nor in the inner medulla was the sum of the concentrations of organic osmolytes affected by the dietary treatment. The sum of sodium, potassium and chloride concentrations did not differ between the two experimental groups, neither in the interstitial nor in the intracellular compartments. However, the urea content and the amounts of HSP25 and HSP72 were significantly lower in the inner medulla of the group of rats fed a high-Na diet. Our results suggest that urea participates in the regulation of the medullary levels of the HSPs and that both HSP25 and HSP72 are components of mechanisms protecting medullary cells against the deleterious effects of high urea concentrations. Received: 30 September 1996 / Received after revision: 30 December 1997 / Accepted: 21 January 1997     

Intrarenal distribution of citrate in the dog during antidiuresis and diuresis

Summary The intrarenal distribution of citrate was evaluated in the dog during antidiuresis and osmotic diuresis, by using the specific citrate assay method of Moellering and Gruber. The measurements were made on tissue samples taken from four different regions throughout the kidney: cortex, outer and inner medulla, and papilla. During antidiuresis, a characteristic distribution of citrate was observed with highest levels in the papilla and lowest ones in the outer medulla. A medullary concentration gradient for citrate was found. Mannitol greatly decreased papillary citrate and sodium, but no changes in outer and inner medullary citrate occured. The results could not be explained by the citrate contained either in the trapped urine or blood in the tissue. It is suggested that citrate accumulation in the inner regions of renal medulla may be accounted for by countercurrent mechanisms or regional differences in renal citrate metabolism.Supported by grants from I.N.S.E.R.M. (n^o 72.1.062.5) and Fondation pour la Recherche Médicale.     

Effects of 0·9% saline infusion on urinary and renal tissue composition in the hydropaenic, normal and hydrated conscious rat

1. Changes in water and solute outputs of hydropaenic, normal and hydrated conscious rats were determined during intravenous infusion (0.2 ml./min) of isotonic (0.9%) saline for 4 hr; renal tissue composition was determined before, and after 1 or 2 hr, infusion.2. In normal and hydrated rats increased excretion of water and sodium was such that urinary output matched intravenous input from about 2 hr. In hydropaenic rats, the diuretic and natriuretic response was much reduced; a retention of infused saline, equivalent to 15% body weight, occurred over 4 hr.3. A considerable increase in urea output and clearance, and a smaller increase in potassium and ammonium outputs, occurred in all groups.4. The corticomedullary osmolal gradients characteristic of non-diuretic rats were largely dissipated during saline infusion: by 1 hr in normal and hydrated rats, and by 2 hr in the hydropaenic group.5. These changes were ascribable mainly to an increase in tissue water content in all segments, particularly in the hydropaenic group; and to a profound decrease in urea content in all groups.6. Changes in tissue sodium content were smaller, and differed between segments and between the differently hydrated groups. A decrease in papillary content occurred in hydropaenic and normal groups and an increase in cortical and outer medullary content occurred in all groups.7. After 2 hr saline infusion, incomplete papillary-urinary osmotic equilibration was evident in all groups.8. These changes in medullary osmolality and in papillary-urinary osmotic equilibration preceded the maximal diuresis, and must contribute to the diuresis induced by saline infusion, as in water and osmotic diureses.     

Mechanisms of impaired urinary concentrating ability in adult rats treated neonatally with enalapril

Neonatal angiotensin-converting enzyme inhibition or angiotensin II type-1 receptor blockade induces irreversible renal histological abnormalities and an impaired urinary concentrating ability in the rat. The aim of the present study was to determine the pathophysiological mechanisms underlying the defect in urine concentration in adult rats treated neonatally with enalapril. Male Wistar rats received daily intraperitoneal injections of enalapril (10 mg kg(-1)) or saline vehicle from 3 to 24 days of age. Assessments of fluid handling and maximal urine osmolality (Uosm(max)), renal function and tubular free water reabsorption (T(c)H2O) under pentobarbital anaesthesia, renal tissue solute concentrations, renal aquaporin-2 (AQP2) expression, and kidney histology, were performed in 12-16-week-old rats. Uosm(max) (1488 +/- 109 vs. 2858 +/- 116 mosm kg(-1), P < 0.05) and maximal T(c)H2O were reduced in enalapril- vs. vehicle-treated rats after administration of 1-desamino-8-D-arginine vasopressin. Neonatally enalapril-treated rats showed marked papillary atrophy, a decrease in medullary tissue solute concentrations, and a reduction in AQP2 expression specifically in the inner medulla. Glomerular filtration rate, renal plasma flow and urinary excretion rates of sodium, potassium and chloride did not differ between groups. In conclusion, adult rats treated neonatally with enalapril showed a urinary concentrating defect of renal origin which primarily could be explained by the papillary atrophy. However, an impaired ability to generate medullary interstitial hypertonicity, and a decrease in inner medullary AQP2 expression, also seem to contribute to this defect.     

The time-course of changes in renal tissue composition during lysine vasopressin infusion in the rat

Summary The corticomedullary osmolal gradient, largely dissipated by sustained water-diuresis, was progressively repleted by continuous i.v. ADH infusion (lysine-vasopressin, 15 mU/min/100 g body weight) in conscious rats for up to 41/2 hr.A marked increase in sodium content was essentially complete by 1/2 hr in the papillary tip; smaller, but more progressive increases occurred in the papillary base and inner medulla. Increases in medullary urea content occurred mainly in the first 21/2 hr, especially in the papillary tip. A progressive decrease in water content of all medullary segments was preceded by a significant papillary tip increase at 1/2 hr.Papillary tip-urine osmotic equilibration was slowly achieved after about 21/2 hr. The small, but significant, tip-urinary urea concentration difference of water diuresis was more rapidly replaced by a substantial difference in the reverse direction.It is concluded that the changes can be explained, adequately, by ADH-induced modifications in water and urea permeabilities of distal nephron segments and, possibly, by changes in inner medullary blood flow; that the evidence of direct ADH stimulation of sodium transport is inconclusive; and that there was no evidence of active urea transport.     

Expression and regulation of αB-crystallin in the kidney in vivo and in vitro

αB-crystallin, a major component of the mammalian eye lens, is a small heat shock protein and molecular chaperone that is also abundant in the mammalian kidney. The present study aimed to characterize more closely the intrarenal expression and regulation of αB-crystallin in vivo and in vitro. In normal rat kidney, the expression of αB-crystallin mRNA and protein were both close to the detection limit in cortex, but increased steeply from the outer to the inner medulla where αB-crystallin constitutes approximately 2% of total tissue protein. Immunohistochemistry disclosed papillary collecting duct cells and thin limbs as the major sites for intrapapillary αB-crystallin immunoreactivity. In rats subjected to sucrose diuresis for 3 days, αB-crystallin mRNA expression was reduced by 27 and 46% in outer and inner medulla, respectively. In agreement with the results obtained in vivo, in Madine–Darby canine kidney cells, αB-crystallin mRNA and protein were induced significantly by elevating the medium osmolality to 500 mosm/kg H₂O by the addition of NaCl and raffinose, and also by urea. The NaCl-induced increase in αB-crystallin expression was concentration-dependently blunted by SP600125, a specific JNK inhibitor. Overexpression of αB-crystallin in 293 cells resulted in increased tolerance to acute osmotic stress. These results indicate that αB-crystallin may be regulated by papillary interstitial tonicity in a JNK-dependent process. Moreover, the high abundance of αB-crystallin in the renal medulla may be important for cell survival in an environment characterized by extreme interstitial solute concentrations as present during antidiuresis.     

The time course of changes in renal tissue composition during mannitol diuresis in the rat

1. The time course and extent of changes in the composition of renal tissue slices in osmotic diuresis were determined by sacrificing groups of rats before and during the intravenous infusion of mannitol (15 g/100 ml.) for up to 7½ hr.

2. Very rapid changes in tissue water and solute contents occurred within 15 min, preceding the times of maximal diuresis, with little subsequent change even up to 7½ hr.

3. The main changes were:

(a) an increase in water content in all slices, particularly the papilla; (b) a very profound decrease in papillary and medullary urea content in the first 15 min, with a small, but significant, further decrease, subsequently; (c) a small, but significant, rapid decrease in papillary sodium, and small non-significant increases in the outer medulla and cortex. Subsequent changes in any segment were small and non-significant; (d) apart from small changes in the first 15 min ammonium and potassium contents remained fairly constant.

4. The rates of change in papillary and urinary urea concentrations were similar, so that after 30 min, any differences between tip and urinary concentrations were small and non-significant.

5. The findings are discussed in terms of factors influencing counter-current mechanisms. It is concluded that altered medullary blood flow is mainly responsible for the rapid changes in medullary composition.

6. The relation between papillary and urinary urea concentrations is explicable in terms of passive handling, with equilibration across a freely permeable collecting duct membrane.

     

Influence of NaCl, urea, potassium and pH on HSP72 expression in MDCK cells

The renal inner medulla is characterised by elevated extracellular concentrations of NaCl, urea, potassium and hydrogen ions, an environment that may affect cell viability negatively. High amounts of HSP72, a stress protein allowing cells to resist harmful situations, are also observed in this region. The present study examined HSP72 induction by various medullary stress factors, individually or in combination, in MDCK cells, a renal epithelial cell line expressing characteristics of the medullary collecting duct. MDCK cells were incubated for 3 days in media containing elevated concentrations of NaCl, urea, potassium and hydrogen ions individually or in combination. HSP72 mRNA and protein expression were determined by Northern and Western blot analyses, respectively. HSP72 expression was enhanced moderately by addition of 50 mM NaCl to normal medium at pH 7.4 but enhanced strongly when added at pH 6.5. The latter degree of HSP72 induction was comparable to that observed when 150 mM NaCl was added at pH 7.4. In normal medium (pH 7.4) containing 300 mM urea, MDCK HSP72 expression was not different from controls. In contrast, urea-induced HSP72 expression was clearly evident when medium pH was lowered to 6.5. Potassium at 20 or 40 mM induced HSP72 only slightly. These results indicate that expression of HSP72 in renal epithelial cells is regulated synergistically by NaCl, urea and pH. Since HSP72 is only slightly induced by increased potassium, this probably reflects the changes in medium osmolality rather than a specific effect of potassium. The high medullary HSP72 content observed even in diuresis may be due to co-operative effects of medullary solutes on HSP72 expression.     

Influence of lysine-vasopressin dosage on the time course of changes in renal tissue and urinary composition in the conscious rat

1. The changes in urinary and renal tissue composition induced by continuous, intravenous infusion of lysine-vasopressin (2.5, 5, 15 and 60 mu-u./min. 100 g body wt.) for up to 4(1/2) hr in water-loaded, conscious rats were determined.2. Both the magnitude of, and the time required to attain, maximal and stable responses, in respect to both urinary and tissue composition, varied with the dose.3. The dose-dependent changes in medullary composition were compounded of graded decreases in water content and graded increases in solute (mainly Na and urea) content.4. The relative contribution of the changes in water, Na and urea contents varied with time and with dose. Significant increases in papillary urea content occurred with all doses. The range of change in urea content was wider than that for any other solute.5. At low doses, the changes in urinary flow and osmolality were ascribable, almost entirely, to large decreases in free-water clearance, with minor changes in medullary composition; at higher doses, the increases in urinary osmolality were accompanied by steep increases in medullary solute concentrations.6. A variable, dose-dependent, transient natriuresis occurred during the phase of increasing medullary Na concentration; the peak natriuresis preceded the times of maximal osmolal and Na concentrations in the papilla and urine.7. The differences in osmolal, urea and Na concentrations between papilla and urine also changed with time.8. Both the transitional and steady-state changes induced by lysine-vasopressin are discussed in terms of intrarenal mechanisms. It is concluded that the data are most reasonably interpreted on the basis that several hormone-sensitive loci exist in the kidneys, each with individual dose-response and kinetic characteristics.     

Time course of changes in renal tissue and urinary composition after cessation of constant infusion of lysine vasopressin in the conscious, hydrated rat

1. The changes in urinary and renal tissue composition in conscious rats were determined for up to 2 hr following the cessation of intravenous infusion of lysine vasopressin, LVP (at 60 muu./min. 100 g body wt. for 4(1/2) hr). A constant water load (4% body wt.) was maintained during and after lysine vasopressin infusion, by quantitative replacement of excreted water. In these circumstances, any changes in urinary and renal tissue composition are presumed to represent direct consequences of the rapid plasma and tissue clearance of lysine vasopressin.2. Urinary flow increased and osmolality decreased, rapidly, reaching stable values characteristic of sustained water diuresis after about 60 min.3. The steepness of the corticomedullary solute concentration gradients also decreased rapidly. Papillary Na and urea concentrations fell to values characteristic of sustained water diuresis in about 45 min.4. The changes in medullary composition were compounded of a moderate significant increase in water content, a moderate, significant decrease in Na content, and a profound decrease in urea content.5. In the eventual steady-state water diuresis, urinary outputs of Na and K were significantly lower, and of NH(4) significantly higher, than those observed in control experiments where LVP infusion was continued for the corresponding 2 hr.6. It is concluded that the diuresis following the cessation of LVP infusion is due not merely to reduced nephron permeability to water but also to a rapid reduction in the osmotic force responsible for water reabsorption from the collecting duct.     

The effect of antidiuretic hormone on the distribution of nephron filtration rates in rats with hereditary diabetes insipidus

Summary The effect of antidiuretic hormone on the distribution of nephron filtration rates was studied in rats with hereditary diabetes insipidus using the Hanssen method for determination of nephron filtration rates as modified by de Rouffignacet al. [18]. Conversion of water diuresis to antidiuresis by infusion of ADH resulted in a moderate, but highly significant increase in the filtration rate of the juxtamedullary nephrons, while the nephrons of all other cortex regions filtered at an unaltered rate. A mechanism based on the action of ADH on distal nephron water permeability is proposed as an explanation: water inflow into the medulla very likely decreases when water diuresis is converted to antidiuresis. This occasions a rise in medullary osmolality which then causes an increase in the apparent viscosity of the blood flowing through the vasa recta. This is responsible for a rise in juxtamedullary postglomerular resistance which results in an increase in the effective filtration pressure and thus in the juxtamedullary nephron filtration rate. The results suggest that an increased juxtamedullary filtration rate participates in the establishment and maintenance of the inner medullary solute gradients, possibly as a consequence of an increased solute delivery to the ascending limbs of the long loops of Henle.This work was supported by the Deutsche Forschungsgemeinschaft.On leave from the University of Melbourne as a recipient of a scholarship from the Deutscher Akademischer Austauschdienst.     

Alterations in renal inner medullary levels of amino nitrogen during acute water diuresis and hypovolaemic oliguria in rats

Levels of total amino compounds (ninhydrinpositive substances, n.p.s.) have been measured in the inner medullas of rats during acute water diuresis and following the induction of hypovolaemic oliguria by the injection (i.p.) of 30% polyethylene glycol 20000 (PEG) in 0.9% saline. Mean medullary fluid n.p.s. concentrations fell from 26.5 mmol to 15.2 mmol Gly equiv/l (–43%) within 2.5 h from the onset of diuresis, while the mean calculated tissue osmolality decreased from 738 mosmol/ kg (control) to 369 mosmol/kg H₂O. By 24 h n.p.s. and osmolality had returned to control levels. By 0.5 h after injection of PEG the mean concentration of n.p.s. had increased from 26.4 mmol to 32.7 mmol Gly equiv/l (+24%) and by 4 h had reached 60.4 mmol Gly equiv/l (+19%). During this time the calculated mean tissue fluid osmolality rose from 696 to 1037 mosmol/kg H₂O. Levels of n.p.s. did not increase further for up to 12 h. It is proposed that losses of amino compounds may make a significant contribution to the overall decrease in medullary cellular osmotic potential accompanying reduced tissue fluid osmolality, and that increased levels of these solutes may provide short-term osmoprotection during antidiuresis of rapid onset, in contrast to the more slowly accumulating methylamines and polyhydric alcohols.     

Role and regulation of glycerophosphorylcholine in rat renal papilla

Glycerophosphorylcholine (GPC) — an organic solute which is considered to be involved in cellular osmoregulation in the renal medulla — was determined by means of an enzymatic assay in various zones of the rat kidney and in papillary tubule suspensions. In antidiuresis, GPC content in cortex, outer medulla and papillary tip was 0.64, 14.6, and 108.9 mmol/kg fresh weight, respectively. Significant concentrations of GPC could not be detected in the urine or in the peripheral plasma. The sharp increase in GPC concentration from cortex to papillary tip was partially abolished by the induction of diuresis by either waterloading or furosemide. These manoeuvres, however, did not change cortical GPC content. Papillary tubule suspensions prepared from hydrogenic rats contained only slightly less GPC per g protein than whole, papillae from antidiuretic animals. Incubation of tubules over 120 min did not lead to a singnificant loss of GPC which is in accordance with the low activity of GPC degrading enzymes in papillary tissue. The results confirm the intracellular localization of GPC and provide further evidence that this substance plays a substantial role in the osmoregulation of renal papillary cells.     

The time course of changes in renal tissue composition during water diuresis in the rat

1. The time course and extent of changes in the composition of renal tissue slices in water diuresis were determined by sacrificing groups of rats before and during the intravenous infusion of dextrose (2.5 g/100 ml.) in amounts sufficient to administer over 2 hr, and subsequently to maintain for up to 7(1/2) hr, a positive fluid load of 4% body weight.2. The corticomedullary osmolal gradient characteristic of the nondiuretic rats was progressively dissipated until, at 7(1/2) hr, only papillary tip concentrations were higher than those of other segments.3. The changes in individual constituents followed different time courses: (i) an increase in water content in all segments, particularly the papilla, was almost complete by 1 hr, preceding the maximal increases in urine flow; (ii) a marked decrease in papillary and medullary urea content in the first hour was followed by a slower, progressive decrease leading to an almost complete dissipation of the urea gradient by 7(1/2) hr; (iii) small, non-significant decreases in sodium content occurred in all segments in the first hr, followed by a further small, progressive decrease in papillary sodium content; (iv) changes in ammonium and potassium concentrations were mainly related to those in water content, since the contents of these solutes showed only small changes.4. By 2 hr, differences in the rates of decline of osmolal and urea concentrations in urine and papilla led to urinary concentrations significantly lower than papillary values. The steep papilla-urine urea concentration difference became smaller, but remained significant even at 7(1/2) hr.5. The findings are discussed in terms of changes in countercurrent mechanisms, particularly as influenced by anti-diuretic hormone.6. The development of papilla/urine urea concentration ratio greater than unity is also considered in terms of passive transport with changes in membrane permeability.     

Evidence for an acid pH in rat renal inner medulla: paired measurements with liquid ion-exchange microelectrodes on collecting ducts and vasa recta

We reevaluated the pH in the renal medulla in rats. pH of the vasa recta blood was about 1 pH unit acidic in comparison to the pH of renal artery blood. During furosemideinduced diuresis pH of vasa recta blood increased whereas pH of collecting duct urine further decreased. The acidic pH in the rat renal inner medulla during antidiuresis raises important questions about the source of H⁺ in inner medulla.     

Mathematical model of mass transport throughout the kidney: Effects of nephron heterogeneity and tubular-vascular organization

A model of transport processes throughout the mammalian kidney is presented. Structural features of the model include labyrinth and medullary ray subsystems in the cortex, distinct vasa recta and capillary plexus subsystems in the outer and inner stripes, and an inner zone subsystem. Distinctions are also made between short and long nephrons, juxtamedullary and nonjuxtamedullary nephrons, vasculature, and interstitial spaces. Salt, urea, plasma proteins, and miscellaneous “nonreabsorbable” solutes in tubular and interstitial fluids are chosen as the essential solutes for describing renal mass transport. Geometric and number density data of vessels are taken from anatomical studies. Membrane parameters are evaluated principally from isolated rabbit tubule perfusion and rat micropuncture experiments. By numerical solution of the mass transport equations, the mild antidiuretic, steady state of a rat is simulated. To assess the importance of special structual features of the model, simulations were performed with different values of the anatomical parameters. By distributing more arterial blood toward the inner cortex and medulla, the osmotic gradient in the inner stripe is reduced while the urinary water and solute excretion rates are increased. When the reabsorption of urea from the papillary collecting duct is enhanced, the interstitial osmotic gradient monotonically increases throughout the inner medulla. This work was supported by a grant to GMS (P.I.) from the National Institutes of Health (AM 26073). PSC held a NIH Predoctoral Traineeship (GM-07535).     

Urea secretion in medullary collecting duct of the rat kidney during water and mannitol diuresis

During steady-state water or mannitol diuresis, the microcatheterization technique was used to study the handling of urea, fluid, sodium, potassium, and total solute along the length of the medullary collecting duct in anesthetized rats. During water diuresis, the remaining fraction of filtered urea increased along the collecting duct as indicated both by regression analysis of all samples and by comparison of paired data from the beginning and end of the duct [(TF/P)urea/In = 43.3 and 50.7%, respectively]. During mannitol diuresis, similar urea entry into the medullary collecting duct was observed, (TF/P)urea/In increasing from 60.7 to 66.5%. Comparison of collecting duct urea handling in proximal and distal segments (beginning to midzone and midzone to papillary tip) suggested that urea entry occurred to a greater extent in the distal portion of the medullary collecting duct. The results demonstrate urea secretion into the medullary collecting duct in diuretic states when urine flow is high and intratubular urea concentration low. Whether urea entry into the collecting duct is an active or passive process cannot be determined from this study, but comparison between urea concentrations in the papillary interstitial fluid and in the urine or tubular fluid raises the possibility of an active urea secretory mechanism in the collecting duct.