Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P41181 (collecting duct)
 5,183 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The renal effects of acyclovir (100 mg/kg body weight i.p. for 7 days) were studied in rats. All animals became polyuric and presented an increase in blood urea nitrogen and fractional excretion of sodium and potassium. During hypotonic saline infusion, the acyclovir-treated rats showed higher distal fractional delivery compared to normal rats (27.8 +/- 4.7 vs. 11.3 +/- 0.9%, p less than 0.01) and a lower ratio of free-water clearance to distal sodium delivery (33.5 +/- 7.8 vs. 57.2 +/- 3.9%, p less than 0.02). Following hypertonic saline infusion, the ratio of osmolar to inulin clearance was higher in acyclovir rats (47.8 +/- 7.4%) than in normal rats (27.0 +/- 4.8%), whereas the ratio of free-water reabsorption to osmolar clearance was lower in the acyclovir rats (13.6 +/- 4.6 vs. 38.2 +/- 3.2%, p less than 0.01). These findings suggest an effect of acyclovir on the proximal tubule, thick ascending limb and/or inner medullary collecting duct (IMCD). In vitro measurements of 3H2O permeability of perfused IMCD of normal rats showed that vasopressin (50 microU/ml) added to the bath increased the diffusional water permeability (43.4 +/- 4.8 vs. 105.6 +/- 9.1 x 10(-5) cm/s), while in acyclovir rats, the control value (58.8 +/- 9.1 x 10(-5) cm/s) did not increase significantly in the presence of vasopressin (71.3 +/- 13.6 x 10(-5) cm/s). These results suggest that high doses of acyclovir produce azotemia and an abnormal function of the proximal tubule and thick ascending limb associated with resistance to vasopressin of the IMCD.
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PMID:Effects of acyclovir on renal function. 143 96

The rabbit papillary surface epithelium (PSE) is a simple cuboidal epithelium that covers the outer surface of the renal papilla and has an apical surface that faces the urinary space. We studied acid-base transport in this epithelium by dissecting it from the papilla, mounting it in a modified Ussing chamber, and following pH changes in the apical bathing solution. The experiments demonstrated that the PSE is capable of acidifying the apical solution at a substantial rate. The acidification rate was similar with 100% nitrogen and 100% oxygen (with and without 10 microM antimycin A), ruling out a dependence on oxidative metabolism. Addition of 1 mM iodoacetate decreased apical acidification by 55%, suggesting a dependence on glycolysis. The net rate of lactate secretion was only 17% of the total acid secretion rate, indicating that apical acidification was not directly caused by secretion of lactic acid alone. Removal of sodium or potassium from the apical solutions or the addition of 1 mM N-ethylmaleimide failed to eliminate the apical acidification. Although the rate of PSE apical acidification is comparable to that of the rabbit outer medullary collecting duct (on a unit surface area basis), its contribution to urinary net acid excretion is likely to be small, owing to the small relative surface area of the PSE. However, by altering the pH of urine locally within the pelvic recesses, the PSE has the potential of modifying the formation of renal stones within the pelvic recesses.
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PMID:Apical acidification by rabbit papillary surface epithelium. 233 Sep 83

Fourteen subjects with persistent azotemia and normal glomerular filtration rate were studied by renal clearances and hormonal determinations to establish the nephron site of altered urea transport and the mechanism(s) responsible for their azotemia. During constant alimentary protein, urea nitrogen appearance was normal and urea clearance was much lower than in 10 age-matched control subjects (23.3 +/- 2.1 ml/min and 49.6 +/- 2.6 ml/min per 1.73 m2, P less than 0.001). Inulin and para-aminohippurate clearances, blood volume and plasma concentration of antidiuretic hormone were within normal limits. During maximal antidiuresis, in spite of greater urea filtered load, the urinary excretion of urea was less, and both the maximum urinary osmolality and the free-water reabsorption relative to osmolar clearance per unit of GFR were greater than in control subjects. After sustained water diuresis, the plasma urea concentration markedly decreased to near normal levels in azotemic subjects. The basal urinary excretion of prostaglandins E2 was significantly reduced in azotemic subjects and was directly correlated with fractional urea clearance (r = 0.857, P less than 0.001). An additional group of control subjects (N = 8) showed a marked reduction of fractional clearance of urea after inhibition of prostaglandin synthesis (P less than 0.01). These data suggest that azotemia is due to increased tubular reabsorption of urea in the distal part of nephron, presumably because of increased back diffusion in the papillary collecting duct, accounting for the enhanced maximum urinary osmolality and free-water reabsorption. Renal prostaglandin E2 may participate in the pathogenesis of azotemia by altering recycling of urea in the medulla.
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PMID:Renal handling of urea in subjects with persistent azotemia and normal renal function. 332

A 52-week toxicity study by oral gavage administration was performed in Sprague-Dawley rats with nefiracetam (N-(2,6-dimethylphenyl)-2-(2-oxo-1-pyrrolidinyl) acetamide, DM-9384, CAS 77191-36-7), a new cognition-enhancing agent, as a part of a safety evaluation program. Dosages of 0 (control), 10, 30, 100 and 300 mg/kg/d were selected for this study. Treatment-related findings were confined to the 300 mg/kg/d level and, to a lesser extent, the 100 and 30 mg/kg/d levels, with the investigations indicating the kidney as the main target organ for toxicity. The microscopic pathology examination of this organ showed papillary epithelial hyperplasia and/or collecting duct epithelial hyperplasia, with cortical scarring and occasional mineralisation in the papilla. Histopathological changes in the liver, centrilobullar hepatocyte enlargement (accompanied by fine vacuolation) and foci/areas of eosinophilic hepatocytes were considered to reflect the induction of drug-metabolising enzymes in the liver. Other tissues showing treatment-related findings included the salivary glands, urinary bladder, spleen, pancreas and adrenals. Additionally, other notable findings included (in the high dosage males only) a decline in body weight (from week 34), lower erythrocytic characteristics and slightly higher plasma urea nitrogen and alkaline phosphatase values. The results in this study, therefore, indicated that the non-toxic effect level was 10 mg/kg/d of nefiracetam.
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PMID:Fifty-two-week oral toxicity study of the new cognition-enhancing agent nefiracetam in rats. 801 94

This study was designed to compare the renal effects of atrial (A-type) natriuretic peptide (ANP) on control (saline-injected) rats and rats with non-oliguric acute renal failure induced by cisplatin. The results obtained here are summarized as follows: (1) In the metabolic cage study, cisplatin-treated rats showed increases in blood urea nitrogen and serum creatinine while creatinine clearance decreased to the lowest levels on day 4. A transient increase in urinary protein was observed at day 4. (2) ANP infusion significantly increased urine flow rate (UFR), creatinine clearance (CCr), fractional excretion rates of sodium (FENa) and chloride (FECl), and urinary phosphorus and magnesium (Mg) excretions in a dose-dependent manner without affecting renal plasma flow and fractional excretion rates of potassium and urea in cisplatin-treated rats. (3) Renal effects of ANP on UFR, CCr, FENa, FECl and excretion of Mg were more pronounced in cisplatin-treated rats compared to control rats although markedly blunted responses to ANP have been reported in nephrotic patients and nephrotic animals induced by adriamycin and aminonucleoside. (4) Histological examination showed extensive necrosis of the S3 segment of the proximal tubule located in the outer stripe of the outer medulla with minimal glomerular abnormalities in the kidney of cisplatin-treated rats. In conclusion, the main mechanism of the increased renal responses to ANP is considered to be due to an increased delivery of sodium, fluid and ANP itself to the inner medullary collecting duct which is the major renal site of action of ANP under the condition of acute proximal tubular necrosis by cisplatin.
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PMID:Renal responses to atrial natriuretic peptide (ANP) in rats with non-oliguric acute renal failure induced by cisplatin. 872 36

Changes in the epithelium thickness of proximal and distal convoluted tubule of cortex, thin descending limb of Henle loop from inner stripe of outer medulla, thick ascending limb from outer stripe of outer medulla and of collecting duct from inner medulla were investigated in young growing sheep fed a low protein diet (LP). Sheep on LP-diet were given a daily ration with 5.73 g of nitrogen and 6.13 MJ of digestible energy (DE) while the daily intake of control group was 19.51 g of N and 12.29 MJ of DE. Both groups of animals were fed these diets at least 6 weeks before collection of kidneys. Morphometric analysis with digitizing tablet showed that intake of LP-diet resulted in significant reduction of epithelium thickness in both distal convoluted tubule and thick ascending limb while the epithelium of collecting duct was found to be thicker. No changes of the epithelium dimensions were determined in proximal tubule and in thin descending limb of Henle loop. Presented results point to the morphological expression of the adaptation of sheep kidneys to a low dietary protein intake which is associated with the increased renal reabsorption of urea.
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PMID:[The effect of a low-protein diet on the epithelium of nephron segments in sheep]. 921 86

Although it has been reported that the circulating adrenomedullin (AM) level is elevated in hypertension and renal failure, the pathophysiological significance of circulating and intrarenal AM in malignant hypertension remains unknown. We investigated the circulating and intrarenal AM system in rats with malignant hypertension by measuring the plasma level, renal tissue level, and mRNA abundance of AM and the mRNA abundance of AM receptor. We also investigated the effects of intravenously infused calcitonin gene-related peptide (CGRP)-(8-37), an antagonist of AM, on the hemodynamics and renal tubular function. We studied the following four groups: control Wistar-Kyoto rats (WKY), control spontaneously hypertensive rats (C-SHR), salt-loaded SHR (S-SHR), and DOCA-salt SHR (D-SHR). After 3 wk of DOCA treatment, D-SHR developed malignant hypertension. D-SHR were characterized by higher blood pressure, kidney weight, urinary protein excretion and blood urea nitrogen, and lower creatinine clearance compared with the other three groups. The plasma AM level and urinary excretion of AM were markedly higher in D-SHR than in the other three groups. In the kidney, the tissue AM level and the expression of AM mRNA in the renal medulla were significantly increased in D-SHR compared with the other three groups, whereas there were no significant differences in these levels in the renal cortex among the four groups. In the renal AM receptor system, the expression of the gene for receptor activity modifying protein 3 was significantly increased in the renal medulla in D-SHR compared with the other three groups. An immunohistochemical study revealed that AM immunostaining in renal collecting duct cells and distal tubules was more intense in D-SHR than in the other three groups. After CGRP-(8-37) infusion, blood pressure increased significantly and urinary sodium excretion and urine flow decreased significantly only in D-SHR. These results suggest that the increased circulating AM and renal AM and the increased expression of the mRNA for AM and its receptor may at least partly compensate for the malignant hypertensive state in certain forms of malignant hypertension via the hypotensive, natriuretic, and diuretic actions of AM.
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PMID:Role of increased circulating and renal adrenomedullin in rats with malignant hypertension. 1170 95

Hypertension caused by angiotensin II is characterized by an increase in tissue oxidant stress as evidenced by increased quantities of reactive oxygen and nitrogen species. Manganese superoxide dismutase (MnSOD) is a key mitochondrial antioxidant enzyme that is inactivated in conditions of oxidant stress by reacting with peroxynitrite to form 3-nitrotyrosine in its active site. The increase in 3-nitrotyrosine content in MnSOD in the kidney of angiotensin II-infused rats was assessed in this study by immunohistochemistry, Western blotting, immunoprecipitation, and HPLC with UV detection (HPLC-UV). MnSOD activity decreased approximately 50% in angiotensin II-infused rat kidneys (24 +/- 4.6 vs. 11 +/- 5.2 U/mg) without a change in protein expression. Immunohistochemical staining showed 3-nitrotyrosine predominantly in distal tubules and collecting duct cells in the angiotensin II-infused rat kidneys. By two-photon microscopy, 3-nitrotyrosine colocalized with MnSOD. Total 3-nitrotyrosine content in kidney homogenates was increased in angiotensin II-infused rat kidney [3.2 +/- 1.9 (sham treated) vs. 9.5 +/- 2.3 ng/mg protein by HPLC-UV detection]. With tracer amounts of tyrosine-nitrated recombinant MnSOD, the most sensitive technique to detect tyrosine nitration of MnSOD was immunoprecipitation from tissue with anti-MnSOD antibody, followed by detection of 3-nitrotyrosine by Western blotting or HPLC. By HPLC, 3-nitrotyrosine content of kidney MnSOD increased 13-fold after angiotensin II infusion, representing an increase from approximately one-twentieth to one-fifth of the total 3-nitrotyrosine content in sham-treated and angiotensin II-infused rat kidney, respectively. Angiotensin II-induced hypertension is accompanied by increased tyrosine nitration of MnSOD, which, because it inactivates the enzyme, may contribute to increased oxidant stress in the kidney.
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PMID:Quantitative assessment of tyrosine nitration of manganese superoxide dismutase in angiotensin II-infused rat kidney. 1279 89

Rodent models of polycystic kidney disease (PKD) have provided valuable insight into the cellular changes associated with cystogenesis in humans. The present study characterizes the morphology of renal and extrarenal pathology of autosomal recessive PKD induced by the wpk gene in Wistar rats. In wpk(-/-) rats, proximal tubule and collecting duct cysts develop in utero and eventually consume the kidney. Increased apoptosis, mitosis, and extracellular tenascin deposition parallel cyst development. Extrarenal pathology occurs in the immune system (thymic and splenic hypoplasia) and central nervous system (CNS; hypoplasia to agenesis of the corpus callosum with severe hydrocephalus). Severity of hydrocephalus varied inversely with size of the corpus callosum. In wpk(-/-) rats, the corpus callosum exhibits relatively few axons that cross the midline. This CNS pathology is similar to that described in three human renal cystic syndromes: orofaciodigital, genitopatellar, and cerebrorenal-digital syndromes. Collecting duct and ventricular ependymal cilia appear morphologically normal. To determine if rodent background strain and the presence of modifier genes affect severity of the disease, we crossed the Wistar-wpk rat with Brown Norway (BN) and Long Evan (LE) rats and found the degree of renal and cerebral pathology was diminished as evidenced by lower kidney weight as a percent of body weight and serum urea nitrogen concentration in cystic rats on LE or BN strains as well as less prominent cranial enlargement. Crosses with BN rats allowed us to localize the wpk gene on chromosome 5 very close to the D5Rat73 marker. The wpk gene lies within a chromosomal region known to harbor a PKD modifier locus. In summary, the types of renal and cerebral pathology seen in the Wistar wpk rat are a unique combination seen only in this rodent model.
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PMID:Development of multiorgan pathology in the wpk rat model of polycystic kidney disease. 1505 65

Members of the Rh glycoprotein family have been shown to be involved in ammonia transport in a variety of species. Here we show that zebrafish Rhcg1, a member of the Rh glycoprotein family, is highly expressed in the yolk sac, gill, and renal tubules. Molecular cloning and characterization indicate that zebrafish Rhcg1 shares 82% sequence identity with the pufferfish ortholog fRhcg1. RT-PCR, combined with in situ hybridization, revealed that Rhcg1 is first expressed in vacuolar-type H(+)-ATPase/mitochondrion-rich cells (vH-MRC) on the yolk sac of larvae at 3 days postfertilization (dpf) and later in vH-MRC-like cells in the gill at 4-5 dpf. Ammonia excretion from zebrafish larvae increased in parallel with the expression of Rhcg1. At larval stages, Rhcg1 mRNA was detected only on the yolk sac and gill; however, the kidney, as well as the gill, becomes a major site of Rhcg1 expression in adults. Using a zebrafish Tol2 transgenic line whose vH-MRC are labeled with green fluorescent protein (GFP) and an antibody against zebrafish Rhcg1, we demonstrate that Rhcg1 is located in the apical regions of 1) vH-MRC on the yolk sac and vH-MRC-like cells (cell population with the expression of Rhcg1 and GFP) in the gill and 2) cells in the renal distal tubule and intercalated cell-like cells in the collecting duct of the kidney. Remarkably, expression of Rhcg1 mRNA at the larval stage was changed by environmental ionic strength. These results suggest that roles of zebrafish Rhcg1 are not solely ammonia secretion to eliminate nitrogen from the gill.
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PMID:Localization of ammonia transporter Rhcg1 in mitochondrion-rich cells of yolk sac, gill, and kidney of zebrafish and its ionic strength-dependent expression. 1768 85


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