Pelvic Epithelium Research Articles

Topography of nitric oxide synthesis by localizing constitutive NO synthases in mammalian kidney

Nitric oxide (NO) is generated from L-arginine by NO synthase (NOS). We have investigated the localization of constitutive NOS isoforms in rat, mouse, guinea pig, rabbit, pig, and human kidney. NADPH diaphorase (NADPH-d) reaction was used for histochemical detection of NOS enzyme activity, neuronal NOS (NOS I) and endothelial NOS (NOS III) were identified by specific antibody, and in situ hybridization was applied for NOS I mRNA detection. Strong presence of NOS I in macula densa (MD), previously detected in rat, was found in all species including humans. Additional NOS I-positive cells of the thick ascending limb (TALH) were defined. A clear-cut distinction between Tamm-Horsfall-protein-positive cells of the TALH and NOS I-positive cells of the TALH was shown. Ultrastructurally, NOS I was located in the cytosol. Intimate spatial relation between NOS I-positive cells and renin-containing preglomerular afferent arteriole suggests an effect of MD-derived NO on the juxtaglomerular granular cells. In the renal vasculature, both NADPH-d and NOS III were located in the endothelium of cortical and medullary vessels, whereas the muscle layer was unreactive. The glomerular arterioles showed stronger labeling in the efferent than in the afferent endothelium, and efferent endothelium selectively contained both NOS I and NOS III. The unique morphology of efferent endothelial cells indicates a particular role for NO in this vessel segment. At the capillary level, only the glomerular tuft showed NOS-positive endothelia. A subpopulation of renal nerves containing NADPH-d and NOS I was found in perivascular connective tissue and near pelvic epithelium. These results demonstrate a wide distribution of two constitutive NOS isoforms in the kidney of various animal species including humans. The distinct location of both isoforms in the cortex confirms that NO plays a crucial role in local glomerular signaling events.

Long-term exposure to the anti-inflammatory agent phenylbutazone induces kidney tumors in rats and liver tumors in mice.

Long‐term toxicity and carcinogenicity of phenylbutazone, a nonsteroidal anti‐inflammatory drug, were evaluated in F344/N rats and B6C3F1 mice. In 2‐year studies, phenylbutazone was given in corn oil by gavage 5 days per week to groups of 50 rats of each sex at doses of 0, 50, or 100 mg/kg body weight, and to groups of 50 mice at doses of 0, 150, or 300 mg/kg body weight. Body weights and survival were similar among groups. Major target organs are kidneys in rats, and liver in mice. Kidney: inflammation, papillary necrosis, and mineralization in both sexes of rats, and hyperplasia and dilatation of the pelvis epithelium, and cysts in female rats. Uncommon tubular cell tumors of the kidney were found in 13 exposed rats: 5 in the 50 mg group and 4 in the 100 mg group of males; 4 in dosed female rats; none in controls. In female rats, dose‐related increases in hyperplasia of the pelvis transitional epithelium, and 2 carcinomas were discovered. Urinary bladder: papillomas of the transitional epithelium were seen in 2 low‐dose male and in 1 low‐dose female rats. Forestomach: ulcers in rats, with acanthosis, hyperkeratosis, and basal cell hyperplasia in female rats; however, no neoplasms were associated with these lesions. Liver: primarily in male mice exposed to. phenylbutazone, hemorrhage, centrilobular cytomegaly and karyomegaly, fatty metamorphosis, cellular degeneration, and coagulative necrosis were seen; clear cell foci were observed in male mice. In summary, under the conditions of these 2‐year oral intubation studies, phenylbutazone is associated with renal carcinogenicity in rats, as evidenced by increases in tubular cell neoplasms in both sexes. Evidence of carcinogenicity for male mice was shown by increased incidences and multiplicity of liver tumors. No carcinogenic activity was found for female mice.

Expression and cellular localization of mRNA encoding the "gastric" isoform of H(+)-K(+)-ATPase alpha-subunit in rat kidney

The distribution of transcripts encoding the gastric H(+)-K(+)-adenosinetriphosphatase (ATPase) alpha-subunit in the normal rat kidney was studied by reverse transcription-polymerase chain reaction (RT-PCR), combined with DNA sequence analysis and renal microdissection, and by nonradioactive in situ hybridization of fixed kidney sections using highly specific molecular probes. RT-PCR products corresponding to the gastric H(+)-K(+)-ATPase alpha-subunit were detected in the cortex, outer and inner medulla, and in isolated cortical (CCD) and inner medullary collecting ducts (IMCD). With digoxigenin-labeled cRNAs derived from the 5' and 3' ends of the gastric H(+)-K(+)-ATPase alpha-subunit cDNA, specific hybridization signal was detected prominently in all the cells of the connecting segment and CCD, the intercalated cells of the outer medullary collecting duct, the IMCD, and the renal pelvic epithelium lining the secondary pouches. Weak labeling was noted in the S3 segment of the proximal tubule, the distal convoluted tubule, and the cortical thick ascending limb of Henle. Hybridization with the sense probes produced no cellular labeling. These data provide the first direct demonstration for the expression and cellular distribution of mRNA encoding the gastric H(+)-K(+)-ATPase alpha-subunit in the normal, potassium-replete kidney, and they provide essential tools for the molecular analysis of renal acid base and potassium transport under physiological and pathophysiological conditions.

Effects of a dietary load of acid or base on changes induced by lactose in rats

Feeding lactose or other slowly digestible carbohydrates to adult mammals may induce a variety of effects including hyperplasia and neoplasia. The most fundamental effect probably is the increased production in the large intestine of short-chain fatty acids (SCFA) resulting from increased fermentation of carbohydrate residues. To find out whether the increased production of these acidic compounds is involved in the induction of certain alterations caused by low-digestibility carbohydrates, the modifying effects of an acidifying (NH 4Cl) or an alkalizing (KHCO 3) diet supplement on lactose-induced changes in rats were studied. Three groups of 50 rats per sex were fed a 20% lactose diet unsupplemented or supplemented with 1% NH 4CI or 2% KHCO 3, for at most 2.5 yr. One control group was fed the basal diet which contained wheat starch instead of lactose. Feeding lactose resulted in wet faecal pellets, reduced pH of the faeces, higher intake of food and water, lower body weights, increased caecal weights and fewer deaths. These effects were not significantly modified by NH 4Cl or KHCO 3. Feeding lactose increased urinary calcium levels, the effect being enhanced by NH 4CI and reduced by KHCO 3. Lactose also tended to increase blood values of alkaline phosphatase and to decrease those for bicarbonate and base excess. These tendencies were generally more marked with NH 4CI, and less marked or absent with KHCO 3. In addition, rats fed lactose showed decreased severity of nephrosis, increased mineralization and hyperplasia of the renal pelvic epithelium, and relatively high incidences of Leydig cell hyperplasia and neoplasia. NH 4Cl supplementation was associated with a relatively small number of single and multiple tumours, with decreased incidences of hyperplasia and mineralization of the renal pelvis epithelium and with a markedly reduced incidence of proliferative changes in the adrenal medulla. With the KHCO 3 supplement the incidences of Leydig cell proliferation and of bladder tumours were relatively high. These findings, in particular the differences between the diet groups in urinary calcium levels and possibly also the variations in blood levels of alkaline phosphatase, bicarbonate and base excess, suggest that the acidic end products of carbohydrate fermentation (SCFA) act as an acid load on the body.

Localization of connexin43 in rat kidney

The localization of connexin43 (Cx 43) in rat kidney was investigated by the indirect immunofluorescence technique with polyclonal antisera raised against Cx 43. Cx 43 is a gap junction protein expressed in a variety of tissues. The typically punctuated gap junction immunofluorescence (GJI) was observed in the renal arterial and arteriolar system. In the renal artery the GJI was concentrated in the media. In the juxtamedullary nephrons, the GJI is particularly abundant in the vascular bundles. There is abundant GJI in the extraglomerular mesangium while in the afferent arteriole GJI appears decreased. Abundant GJI was observed in the inner medullary collecting ducts and pelvic epithelium. The localization of Cx 43 immunofluorescence observed in this study is only in partial agreement with the results of ultrastructural investigations on the distribution of gap junctions in the kidney. An extensive tight junctional system has been demonstrated in the collecting duct system. However, gap junctions have been reported to be absent. Further studies to resolve this discrepancy are required.

Differential expression and cellular distribution of mRNAs encoding alpha- and beta-isoforms of Na(+)-K(+)-ATPase in rat kidney

We have used in situ hybridization histochemistry with isoform-specific, digoxigenin-labeled cRNA probes to characterize systematically the cellular distribution of mRNAs encoding alpha- and beta-subunit isoforms of the Na(+)-K(+)-adenosinetriphosphatase (Na(+)-K(+)-ATPase) in the normal rat kidney. Transcripts encoding the alpha 1-, alpha 2-, alpha 3-, beta 1-, and beta 2-subunits were detected in virtually all of the nephron segments, with prominent hybridization signal in the S3 segment of the proximal tubule, the cortical and medullary thick ascending limb of Henle's loop, the distal convoluted tubule, the cortical collecting duct along its entire length, and the renal pelvic epithelium. Several differences in the cell-specific pattern of expression of the various isoforms were observed. Among the alpha-isoforms, the alpha 3-subunit appeared to be preferentially expressed in the glomerular podocytes and mesangial cells, papillary interstitial cells, and renal pelvic epithelium. The beta-isoforms also differed in their distribution pattern, with the beta 1-subunit expressed to a greater degree in the glomerulus and renal pelvic epithelium and the beta 2-subunit preferentially expressed in the papillary interstitial cells and papillary surface epithelium. The detection and expression pattern of alpha- and beta-subunit mRNAs in structures throughout the kidney is compatible with the possibility of six structurally unique Na(+)-K(+)-ATPase isozymes and suggests a potentially greater role for isozymes comprised of the alpha 2-, alpha 3-, and beta 2-subunits in renal sodium and potassium transport.

The carcinogenic effect of 2,2-dioxopropylnitrosamine on the renal pelvic epithelium of Sprague-Dawley rats, after chronic subcutaneous injections.

The carcinogenicity of 2,2-dioxopropylnitrosamine on the urinary tract was investigated in three experimental groups of Sprague-Dawley rats (15 males, 15 females/group) by weekly subcutaneous administration for the life of the carcinogen at dose levels 1/5, 1/10 and 1/20 of the LD50, and compared with that in a similar group of untreated controls. It resulted in the induction of urinary tract tumours in 42 out of 79 effective animals (53%). Of these animals, 38 developed tumours within the renal pelvis. In the high-dose group, females had a 100% incidence of renal pelvic tumours, and males 73%. In all experimental groups, renal pelvic tumours were more frequent than ureteral and vesical ones. Histologically, the tumours were transitional cell papillomas and carcinomas, except for one squamous carcinoma. Out of 66 tumours, 42 (64%) were low-grade. High-grade tumours arose mainly in the renal pelvis of animals belonging to the highest-dose group. This experiment offers a useful model for the study of mechanisms involved in renal pelvic carcinogenesis.

DNA synthesis and scanning electron microscopic lesions in renal pelvic epithelium of rats treated with bladder cancer promoters

The proliferation response of rat renal pelvic epithelium, lined by transitional epithelium, to administration of various bladder cancer promoters was investigated. In addition, prostaglandin E 2 (PGE 2), lipid peroxide (LPO), malondialdehyde (MDA) and cyclic adenosine 3':5'-monophosphate (cyclic AMP) levels were assessed in urine of rats given the non-promoter l-ascorbic acid (AsA) and the promoters sodium l-ascorbate (AsA-Na) or sodium bicarbonate (NaHCO 3) for 4 or 8 weeks. DNA synthesis in the renal pelvic epithelium, as assessed by 5-bromo-2'-deoxyuridine (BrdU) incorporation, was increased in the groups given AsA-Na, an extremely high dose of sodium chloride (NaCl), tert-butylhydroquinone (TBHQ) or ethoxyquin (EQ). Moreover, with the exception of AsA-Na, ail treatments that induced an elevation of DNA synthesis also caused morphological epithelial alterations as observed by scanning electron microscopy (SEM). Treatment with butylated hydroxyanisole (BHA) and butylated hydroxytoluene (BHT) did not result in any proliferative response of the rat renal pelvis. No treatment-related changes in urinary PGE 2 and cyclic AMP were noted, although AsA-Na and AsA but not NaHCO 3 reduced levels of LPO and MDA in the urine. The results indicate that while the response of renal pelvic epithelium to certain bladder cancer promoters is similar to that of the bladder itself, none of the urinary cellular growth or free radical biochemical parameters is directly related to urothelial cell proliferation.

Subacute and Subchronic Toxicity of Ethylene Glycol Administered in Drinking Water to Sprague-Dawley Rats

Subacute (10-day) and subchronic (90-day) toxicity studies of ethylene glycol (EG) were conducted in male and female Sprague-Dawley rats to provide the U.S. Environmental Protection Agency's (EPA) Office of Drinking Water with toxicity data for final preparation of a Health Advisory for the chemical. Ethylene glycol was administered in drinking water at concentrations of 0.5, 1.0, 2.0, and 4.0% for both sexes in the 10-day study. Based on a projected consumption rate of 100 ml/kg/day, the respective doses on a mg/kg/day basis would be 554, 1108, 2216, and 4432. These dose levels were also used in the 90-day study for females, but dose levels for the males in the 90-day study were 0.25, 0.5, 1.0, and 2.0% (227, 554, 1108, and 2216 mg/kg/day). At time of sacrifice necropsies were performed and tissues were prepared for histological evaluation. Blood samples were taken for hematology and clinical chemistry determinations. Body weights were measured weekly. Water and food consumption were determined three times weekly. No mortality occurred in the 10-day study. In the 90-day study 8/10 females and 2/10 males in the high dose group died prior to sacrifice. Body weights were suppressed in a dose response fashion for males and females. Hemoglobin, hematocrit, erythrocytes, and leukocytes were all significantly decreased in female rats receiving 4% EG for 10 days. The most significant histopathological findings, seen predominantly in males, were kidney lesions which included calcium oxalate crystals in tubules and pelvic epithelium; tubular dilation and degeneration; intratubular proteinaceous material; and inflammation in tubules and pelvic epithelium. At the same dose of ethylene glycol, males had more kidney lesions and much higher incidence and severity of lesions than the females.

Proliferative response of renal pelvic epithelium in rats to oral administration of ortho-phenylphenol, sodium ortho-phenylphenate and diphenyl

Changes in DNA synthesis levels and morphology as observed by scanning electron microscopy (SEM) and light microscopy in rat renal papilla and pelvis following oral administration of ortho-phenylphenol (OPP), sodium ortho-phenylphenate (OPP-Na) and diphenyl, were investigated in F344 rats. OPP and OPP-Na treatment for 4 weeks was associated with elevated DNA synthesis in both renal papilla and pelvis, in addition to distinct morphological cell surface alterations. Sequential light microscope observation revealed induction of renal papillary necrosis from week 4, followed by regeneration hyperplasia at weeks 16 and 24, but no changes in the renal pelvis in the OPP case. OPP-Na not only similarly affected the renal papilla, but also brought about development of hyperplasia in the renal pelvis. No proliferative response of the kidney was apparent in rats fed diphenyl. The present study indicated that the proliferative responses in the renal pelvic epithelium following OPP-Na are similar to those induced by this chemical in the urinary bladder, and that in both cases they are indicative of promoting or carcinogenic potential.

Promotion by sodium barbital of renal cortical and transitional cell tumors, but not intestinal tumors, in F344 rats given methyl(acetoxymethyl)nitrosamine, and lack of effect of phenobarbital, amobarbital, or barbituric acid on development of either renal or intestinal tumors.

Comparative effects of four barbiturates, phenobarbital (PB), amobarbital (AB), sodium barbital (NaBB), and barbituric acid (BA) on the development of neoplasms in the intestinal tract and other organs were investigated in rats following initiation with methyl(acetoxymethyl)nitrosamine (DMN-OAc). Four-week-old F344/NCr male rats were given a single i.p. injection of 0.05 nmol DMN.OAc in 5 ml sterile phosphate buffered saline/kg body weight. Two weeks after DMN.OAc treatment, the animals were provided with either tap water or drinking water containing 500 p.p.m. of PB, NaBB, AB, or BA for the remaining experimental period. Control groups received a single i.p. injection of 5 ml of sterile phosphate buffer/kg body weight and 2 weeks later were given either tap water or drinking water containing 500 p.p.m. of one of the barbiturates listed above. Rats were killed at 52 weeks or 80 weeks after DMN.OAc injection. DMN.OAc induced multiple intestinal tumors that occurred mostly in the mucosa of the small intestine, especially the terminal ileum. None of the barbiturates had any effect on either incidence or multiplicity of intestinal tumors. PB significantly enhanced the development of hepatocellular tumors as well as thyroid follicular cell neoplasms in DMN.OAc initiated rats, while the subsequent administration of NaBB, but not other barbiturates, resulted in the development of renal cortical and pelvic transitional cell tumors. This is the first demonstration of promotion of carcinogenesis in renal pelvic transitional epithelium, a cell type not previously recognized as vulnerable to initiation by DMN.OAc given i.p. NaBB without prior administration of DMN.OAc induced severe nephropathy and focal hyperplasia of both renal cortical tubular and pelvic transitional cell epithelium. No such effects were observed with either PB, AB, or BA. Our results failed to confirm the earlier findings of others that intestinal epithelial carcinogenesis could be promoted by continuous oral administration of NaBB. However, these results strongly support and extend our previous conclusions that some barbiturates have broad organ specificities and promote epithelial carcinogenesis in more than one organ and tissue.

Urea flux in the ureter.

It has been hypothesized that urea from the final urine is recycled into the renal papilla through the pelvic epithelium. To test this hypothesis, samples of urine were collected by micropuncture proximally and distally through the intact, contracting ureter of the anesthetized rat. In 12 rats, in which urine flow was 5.89 +/- 0.67 microliter/min (a moderate antidiuresis), the ratio of proximal-to-distal urea concentration, corrected for water movement, was 0.93 +/- 0.03 (P less than 0.01 compared with unity), indicating that approximately 7% of urea in the urine emerging from the terminal collecting duct was reabsorbed by the time it reached the distal ureter. To assess the possible contribution of urea reabsorption by the ureter, the ureter was cannulated proximally and distally and perfused with urine of known composition at 6.26 +/- 0.10 microliter/min. In nine rats, the ratio of urea concentration in the perfusate collected from the distal end of the ureter to that in the perfusate entering the proximal end was 0.93 +/- 0.02 (P less than 0.01 compared with unity), indicating 7% reabsorption. Movement of solute across the ureteral epithelium was not restricted to urea. Potassium and creatinine were also reabsorbed [3.4 +/- 0.9 (P less than 0.01) and 3.5 +/- 1.2% (P less than 0.05), respectively], whereas sodium was secreted [9.2 +/- 2.3% (P less than 0.01)].(ABSTRACT TRUNCATED AT 250 WORDS)

Hyperkeratotic squamous epithelium of pelvis and ureter in solitary kidney

A case of hyperkeratotic squamous epithelium of the distal renal pelvis and ureter, clinically identifiable as leukoplakia, is reported in a solitary kidney. Because of the need to conserve renal parenchyma in this patient, the lesion was treated conservatively at operation after careful exploration and full thickness biopsy failed to reveal malignancy. Close monitoring of this potentially premalignant lesion has documented no progression at twenty-five months.

Examination of transepithelial exchange of water and solute in the rat renal pelvis.

Severance of the ureter beyond the renal papilla causes a fall in urinary osmolality, which suggests that exchange of water or solute between urine and renal parenchyma normally occurs in the intact renal pelvis. We examined water and solute flux in the renal pelvis with micropuncture and microcatheterization techniques. Four groups of antidiuretic rats were studied. Group I (n = 17) underwent micropuncture through the intact contracting ureter. Urine samples were obtained at the papillary tip, and in the pelvis beside the base of the extrarenal papilla. Urinary osmolality at the base, 880 +/- 97 mosmol/kg H2O (mean +/- SE), was less than that at the tip, 1,425 +/- 104 mosmol/kg H2O (P less than 0.005). In group II (n = 24), samples were analyzed for inulin and osmolality. In 15 rats (group IIA), comparison was made between base and tip samples. In the other nine animals (group IIB), comparisons were made among base, tip, and bladder samples and urea was also measured. In group II (A and B combined) urine-to-plasma (U/P) osmolality was lower at the base, 4.31 +/- 0.27, than at the tip, 6.08 +/- 0.23 (P less than 0.001), and U/P inulin was lower at the base, 192 +/- 25, than at the tip, 306 +/- 16 (P less than 0.001). In group IIB, the bladder urine had a lower U/P osmolality, 5.27 +/- 0.25, than the tip, 6.01 +/- 0.31 (P less than 0.02). The U/P urea was 59 +/- 10.6 (base), 98 +/- 9.4 (tip) (base vs. tip, P less than 0.05), and 81 +/- 6.5 (bladder, P less than 0.005, compared with tip). In group III (n = 8), samples were obtained by microcatheter from the fornices, the deepest intrarenal extensions of the pelvis, and compared with samples at the tip. Urinary osmolality was lower in the fornix, 646 +/- 106 mosmol/kg H2O, than at the tip, 1,296 +/- 99 mosmol/kg H2O (P less than 0.001). Similarly, U/P inulin was lower in the fornix, 48 +/- 14, than at the tip, 128 +/- 12 (P less than 0.001). The lower U/P inulin in the pelvic urine is the result of either the addition of fluid to the pelvis, or the backleak of inulin across the epithelium lining the pelvis. To verify that the pelvic epithelium was impermeable to inulin, in group IVA (n = 4) the left renal pelvis was superfused with a solution of chemical inulin. Cumulative absorption of inulin from the left kidney was 0.15 +/- 0.08% of that superfused. Using [14C]inulin in group IVB (n= 3), similar results were obtained (0.05 +/- 0.02%). These findings indicate that in the renal pelvis, fluid is added to urine after it emerges from the collecting ducts. We suggest that reflux of hyperosmotic urine over the renal papilla creates a transepithelial gradient for the flux of water into the pelvis. A model that incorporates diffusive and convective forces for water and solute transport is proposed to account for these findings.

Recent structure-function relationships in normal and injured mammalian kidneys.

AbstractRecent investigations have been aimed at understanding the ultrastructural‐functional relationships within the kidney at organ, tubule, subcellular, and molecular levels. This has led to a redefinition and more precise segmentation of the renal tubule. For example, the connecting piece between distal tubule and collecting system has now been established.The use of immunocytochemical techniques, such as fluorescence, ferritin‐ or peroxidase‐labelled immunoglobulin methods, has made it possible to identify proteins in the kidney especially in renal corpuscles. Two major noncollagenous glycoproteins, fibronectin and laminin, have now been identified in the glomerulus. The glycosaminoglycan, heparan sulfate, has been localized to the glomerular basement membrane and is thought to play an important role in charge perm‐selectivity during glomerular filtration. Subtle changes in glomerular podocyte or endothelial cell structure are postulated by some to play a role in the pathogenesis of acute renal failure. The role of the mesangial cell in glomerular function is being studied in situ in homogeneous cell populations. These cells are capable of prostaglandin production and can contract in response to hormonal stimulation.The intimate positioning of short‐ and long‐looped nephrons in the renal medulla and the unique nature of the pelvic epithelium correlates well with the purported role of urea recycling in the urinary concentrating mechanism. Determination of elemental concentration of soluble substances in various renal cell and extracellular compartments have been made using freeze‐hydrated and freeze‐dried cryosections of kidney tissue.The medullary and cortical ascending thick limbs of the distal tubule are morphologically and functionally distinct regions. Their response to hormonal stimulation and their enzymatic activities are quite different. Morphological studies of the collecting duct have provided new insight into the role this segment of the uriniferous tubule plays in fluid and electrolyte transport and urinary acidification.

The pelvic epithelium of the rat kidney: a scanning and transmission electron microscopic study.

The renal pelvis of the rat is characterized by extensions called specialized fornices that penetrate into the outer zone of the outer medulla (a type II as classified by Pfeiffer, 1968, 1970). The renal pelvic epithelium, therefore, covers areas of the kidney from the inner medulla, the inner and outer stripe of the outer medulla, and the cortex. The renal pelves of seven rats were studied by transmission and scanning electron microscopy. The transitional epithelium on the nonparenchymal surface of the pelvis was three to four cell layers thick (zone 0-1). This epithelium became thinner where it covered the renal cortex (zone 1-2) or the outer medulla. Although the apical cells of the epithelium retained the asymmetric luminal unit-membrane plaques, the number of cytoplasmic fusiform vesicles decreased as one studied the epithelium progressing over the zones from cortex toward papilla. Scanning electron microscopy demonstrated a small number of surface cells of a different morphology that were characterized by apical microvilli. The number of these microvillous lining cells increased as the epithelium covering the outer (zone 2-3) and inner (zone 3-4) stripe regions of the outer medulla was viewed, until the inner medulla was entirely covered by this cell type. In a reciprocal manner, the cells with the asymmetric apical plaques decreased in numbers and in their morphologic specialization in each successive region. The epithelium surrounding the inner medulla (zone 6-7) was completely devoid of this transitional cell type. Judging from the morphologic characteristics of the epithelia, one could surmise that little exchange of urea, water, and salts would occur with the extrarenal connective tissue or the cortical parenchyma. Recycling of urea might become more important physiologically with the outer stripe parenchyma, and even more so with the increased surfaces of the inner stripe parenchyma that lined the secondary pyramid, as well as with the epithelium lining the medulla.

Spontaneous Bladder and Kidney Lesions in Young Rats

Spontaneous hyperplastic and inflammatory lesions were found in the bladders and kidneys of female rats and their offspring being observed as part of a reproduction study. Bladder lesions consisted of hyperplasia of the mucosal epithelium, mucosal erosion and ulceration, and infiltration of the bladder mucosa with polymorpho-nuclear neutrophils. Kidney lesions included dilation of the renal pelvis, hyperplasia of the pelvic epithelium and inflammation of the renal pelvis (pyelitis). The incidence of these lesions is presented. Spontaneous lesions of this type may affect the interpretation of chemically-induced changes in these organs.

Ultrastructural organization of the hamster renal pelvis.

The renal pelvis of the hamster has been studied by light microscopy (epoxy resin sections), transmission electron microscopy, and morphometric analysis of electron micrographs. Three morphologically distinct epithelia line the pelvis, and each covers a different zone of the kidney. A thin epithelium covering the outer medulla (OM) consists of two cell types: (1) granular cells are most numerous and have apically positioned granules which stain intensely with toluidine blue, are membrane-bound, and contain a fine particulate matter that stains light grey to black in electron micrographs. (2) Basal cells do not have granules, are confined to the basal lamina region, and do not reach the mucosal epithelial surface. The inner medulla (IM) is covered by a pelvic epithelium morphologically similar to collecting duct epithelium of IM. Some cells in this portion of the pelvic epithelium (IM) stain intensely dark with toluidine blue, osmium tetroxide, lead, and uranyl acetate. Transitional epithelium, which separates cortex (C) from pelvic urine, has an asymmetric luminal plasma membrane and discoid vesicles, each of which is similar to those previously observed in mammalian ureter and urinary bladder epithelia. Based on morphological comparisons with other epithelia, the IM and OM pelvic epithelia would appear permeable to solutes and/or water, while the transitional epithelium covering the C appears relatively impermeable. It would also appear that the exchange of solutes and water between pelvic urine and OM would involve capillaries, primarily, since morphometric analysis showed that both fenestrated and continuous capillaries of the OM were extremely abundant (greater than 60% of OM pelvic surface area) just under the thin pelvic epithelium.

Anatomy of the renal pelvis in the hamster

The hamster renal pelvis has been studied by means of low-power light microscopy, scanning electron microscopy and morphometric analyses. The results of this study are highly suggestive that the contact of pelvic urine with the other medulla as well as with the inner medulla may be an important aspect of final urine formation. The outer medulla constituted nearly 50% of the total pelvic surface area, with the inner stripe of the outer medulla more than twice the pelvic surface area of the outer stripe of the outer medulla. The large outer medullary pelvic surface area was accounted for by the elaboration of the upper pelvic walls into peripelvic columns, opercula ("secondary pyramids"), fornices and secondary pouches. A thin simple-squamous to low cuboidal pelvic epithelium separated pelvic urine from outer medullary parenchyma. The inner medulla which constituted about one quarter of the total pelvic surface area was covered by a cuboidal to columnar pelvic epithelium which appeared morphologically similar to the papillary collecting duct epithelium. Tubules and capillaries of the inner medulla did not appear as closely juxtaposed to the pelvic epithelium as did those of the outer medulla. Cortical tissue comprised only 11.7% of the total pelvic surface area and was covered by transitional epithelium similar to that of ureter and bladder. The previously reported impermeability of this epithelium suggests that pelvic urine contact with the cortex is unimportant in final urine formation. The rich layer of smooth muscle under the transitional epithelium probably functions to move urine into and out of the pelvis during pelvic peristalsis, which has been observed in vivo.

Experimental renal infection: Acute and chronic studies of histology and function

Experimental renal infections have resulted in histologic lesions of acute and chronic pyelonephritis, but in most studies the urinary tract has been "traumatized" to induce persistent infection. Sequential functional alterations have been measured infrequently. The present studies were designed to separate the functional and histological changes caused by high pressure sterile reflux from reflux with pathogenic organisms. Reproducible disruption of the pelvic epithelium with extravasation of solution into the parenchyma and vasculature occurred with reflux of 2.0 ml of solution but not with 1.0 ml. Reflux with 2.0 ml of sterile broth failed to cause permanent histologic changes, but reflux with broth containing organisms resulted in minor inflammatory changes. There was no decrease in renal function in either group. In long-term studies, no histologic changes in the cortex or medulla were noted 21 weeks after reflux of 1.0 ml of broth containing organisms; however, there was failure of functional maturation in the infected animals commensurate with their growth, as compared to the shams and controls (P = 0.03). Sterile reflux did not cause cortical scars or changes in renal function, but persistent parenchymal infection was associated with arrest of functional growth.