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PubMed1985

Morphologic and functional evidence for oxygen deficiency in the isolated perfused rat kidney.

Morphologic and functional studies were undertaken in the isolated rat kidney, perfused with an albumin-Krebs-Henseleit solution, to which 5% human erythrocytes and/or various amino acids had been added. Perfused only with the albumin-Krebs-Henseleit solution, the kidneys displayed a characteristic pattern of cell necrosis after 2 hours of perfusion, which was confined to the interbundle region of the outer medulla and was not evident in either the cortex or the inner medulla. In the outer stripe only those proximal straight tubules (P3 segments) farthest from the vascular bundles were damaged. In the inner stripe only those thick ascending loops of Henle at the periphery of the vascular bundles escaped damage; all thick ascending loops of Henle lying farthest from the bundles were severely damaged. The number of damaged tubules increased toward the border to the inner medulla. Necroses in both segments, P3 and thick ascending loops of Henle, could be prevented by perfusion with the erythrocyte-albumin-Krebs-Henseleit solution but not by the addition of glutathione, in the absence of erythrocytes. Perfusion with the erythrocyte medium also significantly improved glomerular filtration rate and sodium and glucose reabsorption. It is concluded that, in the isolated, erythrocyte-free perfused kidney, the oxygen content of the "arterial" vasa recta in the vascular bundles is only sufficient to supply the tubules in the immediate surroundings. Countercurrent exchange in the vascular bundles between arterial and "venous" vasa recta progressively lowers the arterial oxygen content as the inner stripe of the outer medulla is approached and with it the number of tubules receiving an adequate oxygen supply.

Animals↗
PubMed1996

Permeability criteria for effective function of passive countercurrent multiplier.

The urine concentrating effect of the mammalian renal inner medulla has been attributed to countercurrent multiplication of a transepithelial osmotic difference arising from passive absorption of NaCl from thin ascending limbs of long loops of Henle. This study assesses, both mathematically and experimentally, whether the permeability criteria for effective function of this passive hypothesis are consistent with transport properties measured in long loops of Henle of chinchilla. Mathematical simulations incorporating loop of Henle transepithelial permeabilities idealized for the passive hypothesis generated a steep inner medullary osmotic gradient, confirming the fundamental feasibility of the passive hypothesis. However, when permeabilities measured in chinchilla were used, no inner medullary gradient was generated. A key parameter in the apparent failure of the passive hypothesis is the long-loop descending limb (LDL) urea permeability, which must be small to prevent significant transepithelial urea flux into inner medullary LDL. Consequently, experiments in isolated perfused thin LDL were conducted to determine whether the urea permeability may be lower under conditions more nearly resembling those in the inner medulla. LDL segments were dissected from 30-70% of the distance along the inner medullary axis of the chinchilla kidney. The factors tested were NaCl concentration (125-400 mM in perfusate and bath), urea concentration (5-500 mM in perfusate and bath), calcium concentration (2-8 mM in perfusate and bath), and protamine concentration (300 micrograms/ml in perfusate). None of these factors significantly altered the measured urea permeability, which exceeded 20 x 10(-5) cm/s for all conditions. Simulation results show that this moderately high urea permeability in LDL is an order of magnitude too high for effective operation of the passive countercurrent multiplier.

Animals↗
PubMed2000

Functional morphology of the avian medullary cone.

The organization of the renal medulla of the Gambel's quail, Callipepla gambelii, kidney was examined to determine the number of loops of Henle and collecting ducts and the surface area occupied by the different nephron segments as a function of distance down the medullary cones. Eleven medullary cones were dissected from the kidneys of four birds, and the tissue was processed and sectioned for light microscopy. In addition, individual nephrons were isolated on which total loop thin descending segment and thick prebend segment lengths were measured. The results show no correlation between the absolute number of loops of Henle and the length of the medullary cones. The number of thick and thin limbs of Henle and collecting ducts decrease exponentially with distance toward the apex of the cones and the rate of decrease is similar for cones of different lengths. Initially there is a rapid decrease in the number of thin limbs of Henle, indicating that most nephrons do not penetrate the cones a great distance. Thick descending limbs of Henle (prebend segment) ranged in length from 50 to 770 microm, and there was little correlation with the total length of the loop of Henle. However, the length of the thin limb of Henle correlated well with total loop length. The cell surface areas of the limbs of the loop of Henle and the collecting ducts decreased toward the apex of the cones.

Animals↗
PubMed1983

Deep nephron and collecting duct function after unilateral reduction in renal mass.

Papillary micropuncture was used to study juxtamedullary nephron and terminal collecting duct function in the remnant kidney when the contralateral kidney was present. Urine osmolality from the remnant kidney was significantly lower than that measured for the control kidney. Surface nephron function appeared unaffected by remnant formation. Delivery of water to the bend of the loop of Henle of deep nephrons was increased. It is proposed that part of this increase in delivery is a consequence of a decrease in water extraction along the descending limb of the loop of Henle. Surprisingly, there was a decrease in fractional sodium delivery to the bend of the loop of Henle. This suggests enhanced fluid reabsorption in the proximal segments of deep nephrons. Water and sodium reabsorption along the terminal segment of the collecting duct was not affected by remnant formation. However, fluid osmolality measured along this segment was lower than that obtained in controls. Values obtained along the descending limb of the loop of Henle of deep nephrons did not differ from collecting duct fluid. This suggests no significant alteration in collecting duct permeability. Rather, the findings of the present study suggest that the lower osmolality of the final urine may be due, in part, to a reduction in the deposition of sodium in the papillary interstitium.

Absorption↗
PubMed1989

Dependency of microdissected nephron segments upon oxidative phosphorylation and exogenous substrates: a relationship between tubular anatomical location in the kidney and metabolic activity.

1. In order to examine the possibility of heterogeneity in the dependence of renal tubular cells upon oxidative phosphorylation and exogenous substrates, the effects of antimycin A and substrate deprivation on adenosine 5'-triphosphate (ATP) content were examined in isolated rat nephron segments in vitro at 37 degrees C. 2. Antimycin A (5 mumol/l) caused varying decrements in cell ATP level within 5 min in the following order: proximal tubules greater than cortical thick ascending limb of Henle's loop (cTAL) greater than cortical collecting duct (cCD) in the cortex, and thin descending limb of Henle's loop (TDL) greater than medullary thick ascending limb of Henle's loop (mTAL) greater than outer medullary collecting duct (omCD) in the inner stripe of the outer medulla. In the thick ascending limb and the collecting duct, the segments located in the cortex were more sensitive than those in the medulla. 3. Substrate deprivation for 30 min markedly decreased the cell ATP content in cortical and medullary proximal tubules and also in medullary TDL, whereas it caused only a slight decrease in cTAL and mTAL with no change in cCD and omCD. 4. Media made hypertonic by the addition of 200 mmol/l NaCl under aerobic conditions, increased the requirement for exogenous substrates in TDL and mTAL, but not in omCD. This stimulation was seen to a lesser extent in media made hypertonic by the addition of mannitol instead of NaCl.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗
PubMed1984

Segmental analysis of renal glucose transport in young female rats.

Free-flow micropuncture studies were performed on twenty-seven young female Sprague-Dawley rats before and after 10% extracellular volume expansion to evaluate glucose reabsorption at the accessible sites of both surface and papillary nephrons. In the distal nephron segments no significant glucose reabsorption was observed for the distal tubule and papillary collecting duct but significant difference in fractional glucose delivery was demonstrated between the bend of the Henle's loop and early distal tubule and between the late distal tubule and the base of the collecting duct. Comparison of the fractional glucose delivery within the same nephron group for both superficial and juxtamedullary nephrons indicated that glucose reabsorption occurred at some sites beyond the bend of the Henle's loop. Volume expansion inhibited glucose reabsorption in the proximal convoluted tubule, enhanced it in the segment between the late proximal and early distal tubules, but had no effect on glucose transport at further distal sites. It is concluded that, in addition to the proximal tubule, the ascending loop of Henle or cortical collecting tubule may play a role in maintaining glucose-free urine under physiological conditions.

Absorption↗
PubMed1995

Tamm-Horsfall glycoprotein in streptozotocin diabetic rats: a study of kidney in situ hybridization, immunohistochemistry, and urinary excretion.

Tamm-Horsfall glycoprotein, present only in the kidney thick ascending limb of Henle's loop, was studied here in streptozotocin diabetic rats. Tamm-Horsfall glycoprotein mRNA in situ hybridization was performed on snap-frozen left kidneys; the right kidneys were perfusion-fixed with 4% paraformaldehyde and embedded either in paraffin, for Tamm-Horsfall glycoprotein immunohistochemistry, or in Epon for stereologic measurements. The length of the thick ascending limb of Henle's loop and the amount of glycogen were measured and the ultrastructure of the cells was evaluated. Urinary excretion of Tamm-Horsfall glycoprotein, calcium, magnesium and albumin was measured. After 10 and 50 days' duration of diabetes, kidney weight increased 20 and 41%, respectively and the length of the thick ascending limb of Henle's loop increased 28 and 56%, respectively, compared with controls. Substantial glycogen accumulations were present in the thick ascending limb of Henle's loop, and electron microscopy revealed a significant decrease in organelles and basolateral membranes. After 10 and 50 days' duration of diabetes, in situ hybridization of Tamm-Horsfall glycoprotein mRNA revealed a fourfold decrease, and the immunostaining for Tamm-Horsfall glycoprotein showed a threefold decrease as measured by densitometry. However, urinary Tamm-Horsfall glycoprotein excretion rate was increased fivefold and urinary concentration about twofold. Urinary calcium excretion increased three-fold and magnesium twofold, but urinary albumin excretion was not significantly increased. The increased amount of Tamm-Horsfall glycoprotein, calcium and magnesium in the urine in diabetes occurs here concomitant with severe cellular damage in the thick ascending limb of Henle's loop.

Albuminuria↗
PubMed1979

The clinical physiology of water metabolism. Part II: Renal mechanisms for urinary concentration; diabetes insipidus.

The renal reabsorption of water independent of solute is the result of the coordinated function of the collecting duct and the ascending limb of the loop of Henle. The unique juxtaposition of the ascending and descending portions of the loop of Henle and of the vasa recta permits the function of a counter-current multiplier system in which water is removed from the tubular lumen and reabsorbed into the circulation. The driving force for reabsorption is the osmotic gradient in the renal medulla which is dependent, in part, on chloride (followed by sodium) pumping from the thick ascending loop of Henle. Urea trapping is also thought to play an important role in the generation of a hypertonic medullary interstitium. Arginine vasopressin (AVP) acts by binding to receptors on the cell membrane and activating adenylate cyclase. This, inturn, results in the intracellular accumulation of cyclic adenosine monophosphate (AMP) which in some fashion abruptly increases the water permeability of the luminal membrane of cells in the collecting duct. As a consequence, water flows along an osmotic gradient out of the tubular lumen into the medullary interstitium. Diabetes insipidus is the clinical condition associated with either a deficiency of or a resistance to AVP. Central diabetes insipidus is due to diminished release of AVP following damage to either the neurosecretory nuclei or the pituitary stalk. Possible causes include idiopathic, familial, trauma, tumor, infection or vascular lesions. Patients present with polyuria, usually beginning over a period of a few days. The diagnosis is made by showing that urinary concentration is impaired after water restriction but that there is a good response to exogenous vasopressin therapy. Nephrogenic diabetes insipidus can be identified by a patient's lack of response to AVP. Nephrogenic diabetes insipidus is caused by a familial defect, although milder forms can be acquired as a result of various forms of renal disease. Central diabetes insipidus is eminently responsive to replacement therapy, particularly with dDAVP, a long lasting analogue of AVP. Nephrogenic diabetes insipidus is best treated with a combination of thiazide diuretics as well as a diet low in sodium and protein.

Body Water↗
PubMed1993

Recent studies on the characterization of loop diuretics.

This article provides a survey of transport mechanisms in the loop of Henle and of secondary effects on electrolyte excretion of loop diuretics. Results are presented of experiments that define ion transport in the thick ascending limb. New data on ion channels and transport regulation in this tubule segment are summarized. In addition, the mechanisms underlying enhanced sodium chloride and water transport after diuretics in tubule segments that are located downstream of the loop of Henle are surveyed. Finally, the effects of K depletion and chronic metabolic acidosis on diuretic potency of torasemide as well as possible antialdosterone effects of torasemide are evaluated.

Animals↗
PubMed1982

Further evidence for an inverse relationship between macula densa NaCl concentration and filtration rate.

It has been concluded that tubulo-glomerular feedback mechanism is triggered by changes in NaCl concentration ([NaCl]) at the macula densa. This conclusion is based on the demonstration that changes in filtration rate produced during retrograde perfusion of the loop of Henle depend upon the perfusate [NaCl]. Experiments were performed to evaluate whether the effect on glomerular function of orthograde perfusion of the loop of Henle is consistent with this conclusion. Early proximal flow rate (VEP), stop-flow pressure (PSF), early distal chloride concentration ([C]), and flow rate were measured during perfusion of the loop of Henle with mannitol solution (300 mosm kg-1), 30mM NaCl + mannitol (300 mosm kg-1), 140 mM Na isethionate and artificial tubular fluid. When distal flow exceeded 10 nl min-1, the magnitude of the glomerular response was predictable from the [Cl]. The linear regression line, delta VEP = -0.27 [Cl] + 4.3, did not differ from that obtained previously with the retrograde technique. Retrograde perfusion with 140 mM Na isethionate was without effect on VEP. We conclude that the effect on glomerular function of perfusion of the loop of Henle in either an orthograde or a retrograde direction with these solutions depends upon the chloride concentration at the macula densa.

Animals↗
PubMed1976

Activation of tubulo-glomerular feedback by chloride transport.

To define the luminal agent(s) responsible for the reduction of nephron filtration rate following increases of loop of Henle flow rate early proximal flow rate (EPFR) during loop perfusion with 17 different salt solutions were compared to the non-perfused tubules. During orthograde microperfusions a reduction of EPFR as indication of a feedback response was noted with a number of monovalent Cl- and Br- salts (LiCl, KCl, NaCl, RbCl, CsCl, NH4Cl, choline Cl, NaBr, KBr), with Na+ salts except Na acetate (NaHCO3, NaNO3, NaF, NaI, NaSCN), and with CaCl2 and MgCl2. These latter 2 solutions where used in a concentration of 70 mM while all other solutions had a concentration of 140 mM. During retrograde perfusion from the distal to the proximal end of the loop of Henle EPFR fell significantly with Cl- and Br- salts with percentage changes of EPFR ranging from -8.0 to -44.3%. In contrast, Cl- free salts and Cl- salts of divalent cations were associated with percentage changes of EPFR ranging from +7.1 to -6.2%, significance being reached only during perfusion with NaSCN. When furosemide (5 x 10(-4) M) was added to NaBr or KBr a feedback response was not observed. During orthograde perfusion with NaNO3 distal Cl- concentrations were 44.2 +/- 5.08, mM (mean +/- S.E.) at a perfusion rate of 10 nl/min and 59.1 +/- 3.93 mM at a rate of 40 nl/min. CaCl2 perfusion induced a marked elevation of distal Cl- concentrations to levels higher than 140 mM. Loop chloride handling was normal during RbCl perfusion. The magnitude of the feedback response during retrograde perfusion was not changed by lowering NaCl concentration from 140 to 60 mM, but fell when NaCl concentration was further reduced. In contrast to orthograde perfusions it was insensitive to changes in flow rate. Our results are compatible with the thesis that feedback responses depend critically upon the rate of Cl- transport probably across the macula densa cells. Br- ions can replace Cl- because they appear to share a common transport pathway which can be inhibited with furosemide. Unspecificity of feedback responses during orthograde microperfusions is due to presence of Cl- ions in the macula densa region even when solutions are initially Cl- free. Cl- salts of divalent cations do not elicit a feedback response because Cl- transport is severely curtailed.

Animals↗
PubMed1981

Ultrastructural studies of tubulointerstitial immune complex nephritis in rats immunized with Tamm-Horsfall protein.

Rats immunized with Tamm-Horsfall protein, a surface membrane glycoprotein of cells of the ascending thick limb of Henle's loop, develop autoantibodies to Tamm-Horsfall protein and a tubulointerstitial nephritis selectively involving the thick ascending limb of Henle's loop. The localization of the immune deposits formed in this model was studied by transmission electron microscopy. The frequency, size, and distribution of electron-dense deposits closely paralleled that of granular and nodular deposits of rat IgG, C3, and Tamm-Horsfall protein at the base of the cells of the ascending thick limb of Henle's loop. The earliest electron-dense deposits were present in the extracellular space between basal infoldings of cell membranes and the tubular basement membranes. In the more advanced lesions, the larger electron-dense deposits were also present within the tubular basement membranes and between tubular cell membranes displacing tubular structures. Selective mononuclear cell infiltration around these tubules with deposits in this model of tubulointerstitial nephritis suggests that antibodies to Tamm-Horsfall protein cross tubular basement membranes and form immune complexes in situ by combining with the Tamm-Horsfall protein molecules of basal cell surface membranes.

Animals↗
PubMed1981

Structural organization of the renal medulla: comparative and functional aspects.

The renal medulla develops very differently among species, being more prominent in those with a high urinary concentrating capacity. Attempts to correlate structure and function must consider loops of Henle, collecting ducts, vessels, interstitium, and pelvis. Two types of loops of Henle, long and short, are distinguished. Numerical relationships between both differ among species. Based on the epithelial lining a short loop consists of a thick descending limb (pars recta of proximal tubule), a thin descending limb, and a thick ascending limb. Long loops, in addition, have a thin ascending limb; their descending thin limbs are different from those of short loops and are site of considerable interspecies differences. Collecting ducts form in the cortex by joining several nephrons. Patterns with and without arcade formation are distinguished. On entering inner medulla, collecting ducts fuse successively. Collecting duct epithelium consists of principal and intercalated cells whose individual functions are subject to debate. Blood vessels are arranged in a very strict pattern reflecting that, in addition to nourishment, unique requirements in maintaining the corticomedullary osmotic gradient are to be met. Ultrastructural organization of medullary vessels is less specific compared to cortical vessels. Two types of renal medulla are distinguished. The simple type has vascular bundles consisting only of de- and ascending vasa recta; in the complex type, descending thin limbs of short loops are also integrated into vascular bundles. Functional implications of this difference are considerable. Striking interspecies differences also occur in the renal pelvis.

Animals↗
PubMed1982

Immunocytochemical localization of Na+, K+-ATPase in the rat kidney.

To determine if rat kidney Na+, K+-ATPase can be localized by immunoperoxidase staining after fixation and embedding, we prepared rabbit antiserum to purified lamb kidney medulla Na+, K+-ATPase. When sodium dodecylsulfate polyacrylamide electrophoretic gels of purified lamb kidney Na+, K+-ATPase and rat kidney microsomes were treated with antiserum (1:200), followed by [125I]-Protein A and autoradiography, the rat kidney microsomes showed a prominent radioactive band coincident with the alpha-subunit of the purified lamb kidney enzyme and a fainter radioactive band which corresponded to the beta-subunit. When the Na+, K+-ATPase antiserum was used for immunoperoxidase staining of paraffin and plastic sections of rat kidney fixed with Bouin's, glutaraldehyde, or paraformaldehyde, intense immunoreactive staining was present in the distal convoluted tubules, subcapsular collecting tubules, thick ascending limb of the loops of Henle, and papillary collecting ducts. Proximal convoluted tubules stained faintly, and the thin portions of the loops of Henle, straight descending portions of proximal tubules, and outer medullary collecting ducts did not stain. Staining was confined to basolateral surfaces of tubular epithelial cells. No staining was obtained with preimmune serum or primary antiserum absorbed with purified lamb kidney Na+, K+-ATPase, or with osmium tetroxide postfixation. We conclude that the basolateral membranes of the distal convoluted tubules and ascending thick limb of the loops of Henle are the major sites of immunoreactive Na+, K+-ATPase concentration in the rat kidney.

Animals↗
PubMed1983

Effect of carbonic anhydrase inhibition on superficial and deep nephron bicarbonate reabsorption in the rat.

The nephron segment responsible for the acetazolamide-insensitive fraction of renal bicarbonate reabsorption has not been clearly delineated. This study compares superficial and deep nephron bicarbonate reabsorption before and after acetazolamide at two dose levels (20 and 50 mg/kg per h) in mutant Munich-Wistar rats employing both cortical and papillary micropuncture and microcalorimetry. Systemic acid-base balance and right whole kidney glomerular filtration rate were similar in all groups examined. The effects of the two doses of acetazolamide were indistinguishable and resulted in a significant increase in whole kidney bicarbonate excretion that compared favorably with the fraction delivered out of the left papillary tip. Acetazolamide inhibited superficial proximal bicarbonate reabsorption by 80.0%, whereas reabsorption up to the deep loop of Henle was decreased by only 52% (P less than 0.001). Bicarbonate reabsorption that was insensitive to acetazolamide occurred in the superficial and deep loop of Henle and between the distal tubule and base collecting duct. Because water reabsorption in these segments could serve to generate transepithelial bicarbonate concentration gradients favorable for reabsorption, we attempted to minimize water abstraction by combined administration of mannitol and acetazolamide. During this condition a significant increase in bicarbonate delivery up to the deep loop of Henle was noted (52 vs. 65%), whereas superficial nephron reabsorption was not altered. Furthermore, an outwardly directed bicarbonate concentration gradient from the deep loop of Henle to vasa recta was demonstrated during acetazolamide (delta tCO2 = 20.9 +/- 3.3 mM), but was abolished during combined mannitol and acetazolamide administration (delta tCO2 = 3.5 +/- 0.9 mM). It is concluded that carbonic anhydrase inhibition results in a disparate effect on nephron bicarbonate reabsorption when juxtamedullary and superficial nephron segments are compared. Our findings suggest that a mechanism for residual bicarbonate reabsorption during acetazolamide administration may be passive reabsorption driven by favorable transepithelial concentration gradients.

Acetazolamide↗
PubMed1976

The distribution of leptospires in the kidney tubules of some British wild mammals.

Histological examination of 69 pairs of infected kidneys from 12 species of Rodentia, Lagomorpha, Carnivora and Insectivora revealed that leptospires were confined mainly to the proximal and distal convoluted tubule, were less often found in the thick loop of Henle and only rarely in the collecting duct. On no occasion were the organisms present in the thin loop of Henle. Preliminary observations on the relationship of leptospires to tubule epithelium indicate some degree of physical attachment. It is suggested that the avoidance of the thin loop of Henle might be a reflection of its structural properties.

Animals↗
PubMed1988

Resetting of tubuloglomerular feedback in acute volume expansion in rats.

Loss of sensitivity or "resetting" of tubulo-glomerular feedback has been reported after both acute and chronic volume expansion in rats. In chronic volume expansion due to dietary salt loading, resetting was found to result from the appearance of an inhibitory factor in tubular fluid. The aim of the present study was to test the possibility that resetting after acute isooncotic volume expansion may also be due to such an inhibitor. Rats were acutely volume expanded (4.5% of body weight) by infusion of a solution of fresh plasma and Ringer's solution. Tubuloglomerular feedback activity was assessed in expanded and control animals by measuring early proximal flow (EPF) rate during perfusion of the loop of Henle at varying rates with proximal tubular fluid harvested from the control (control TF) and expanded animals (AVE TF). When loops of Henle in control animals were perfused with control TF at 10, 20 or 40 nl min-1, EPF fell from (mean +/- SD) 29.8 +/- 5.6 at zero loop flow to 27.5 +/- 7.5, 21.1 +/- 4.2 and 15.5 +/- 4.5 nl min-1 gKW-1 respectively. Perfusion at the same rates with control TF in expanded animals reduced EPF from 39.5 +/- 9.6 (at zero loop flow) to 35.9 +/- 11.3, 31.6 +/- 4.3 and 22.9 +/- 6.8 nl min-1 gKW-1 respectively. When loops of Henle in control animals were perfused with AVE TF, EPF fell from 28.6 +/- 9.5 (zero loop flow) to 23.5 +/- 8.6, 19.9 +/- 8.2 and 15.6 +/- 6.5 nl min-1 gKW-1 respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2002

Expression of aldose reductase in developing rat kidney.

Newborn rats are not capable of producing concentrated urine. With development of the concentrating system and a hypertonic medullary interstitium, intracellular osmolytes, such as sorbitol, accumulate in the renal medulla. Sorbitol is produced from glucose in a reaction catalyzed by aldose reductase (AR). The purpose of this study was to establish the time of expression and distribution of AR in the developing rat kidney. Kidneys from 16-, 18-, and 20-day-old fetuses and 1-, 3-, 4-, 5-, 7-, 14-, and 21-day-old pups were processed for immunohistochemistry and immunoblot analysis. In adult animals, AR was expressed only in the inner medulla, in which it was localized in ascending thin limbs (ATLs), inner medullary collecting ducts (IMCDs), and interstitial cells. AR immunoreactivity was not detected in fetal kidneys but was observed in the terminal part of the descending thin limb and IMCD in the renal papilla of 1-day-old pups. At birth, all of the loops of Henle are configured as short loops and there are no ATLs. After birth, papillary thick ascending limbs are gradually transformed into ATLs by a process that involves apoptotic deletion of cells from the thick ascending limb. During this time, AR immunoreactivity appeared in the cells undergoing transformation in the ascending limb, beginning at the papillary tip and ascending to the border between the outer medulla and the inner medulla. However, there was no labeling of apoptotic cells. The expression of AR in both the ATL and the IMCD gradually increased during kidney development. We conclude that AR expression in the inner medulla coincides with the increase in medullary tonicity that is known to occur during the first 3 wk after birth. On the basis of the observation that only AR-negative cells were deleted by apoptosis in the differentiating ATL, we propose that AR may protect ATL cells against apoptosis.

Aging↗