Upregulation of Na+ transporter abundances in response to chronic thiazide or loop diuretic treatment in rats

2003 ◽  
Vol 284 (1) ◽  
pp. F133-F143 ◽  
Author(s):  
Ki Young Na ◽  
Yoon Kyu Oh ◽  
Jin Suk Han ◽  
Kwon Wook Joo ◽  
Jung Sang Lee ◽  
...  
Keyword(s):  
Tap Water ◽  
Chronic Administration ◽  
Thick Ascending Limb ◽  
Sprague Dawley ◽  
Volume Depletion ◽  
Diuretic Treatment ◽  
Sprague Dawley Rats ◽  
Collecting Ducts ◽  
Site Of Action

Furosemide and hydrochlorothiazide (HCTZ) exert their diuretic actions by binding to apical Na+ transporters, viz., the Na+-K+-2Cl− cotransporter in the thick ascending limb and the Na+-Cl−cotransporter in the distal convoluted tubule, respectively. We carried out semiquantitative immunoblotting and immunohistochemistry of rat kidneys to investigate whether chronic administration of furosemide or HCTZ is associated with compensatory changes in the abundance of Na+ transporters downstream from the primary site of action. Osmotic minipumps were implanted into Sprague-Dawley rats to deliver furosemide (12 mg/day) or HCTZ (3.75 mg/day) for 7 days. To prevent volume depletion, all animals were offered tap water and a solution containing 0.8% NaCl and 0.1% KCl as drinking fluid. The diuretic/natriuretic response was quantified in response to both agents by using quantitative urine collections. Semiquantitative immunoblotting revealed that the abundances of thick ascending limb Na+-K+-2Cl− cotransporter and all three subunits of the epithelial Na+ channel (ENaC) were increased by furosemide infusion. HCTZ infusion increased the abundances of thiazide-sensitive Na+-Cl−cotransporter and β-ENaC in the cortex and β- and γ-ENaC in the outer medulla. Consistent with these results, β-ENaC immunohistochemistry showed a remarkable increase in immunoreactivity in the principal cells of collecting ducts with either diuretic treatment. These increases in the abundance of Na+transporters in response to chronic diuretic treatment may account for the generation of diuretic tolerance associated with long-term diuretic use.

Chemopreventive effect of diclofenac on mammary carcinogenesis in Sprague-Dawley rats

Biologia ◽  
2013 ◽  
Vol 68 (4) ◽  
Author(s):  
Peter Orendáš ◽  
Ivan Ahlers ◽  
Bianka Bojková ◽  
Monika Kassayová ◽  
Peter Kubatka ◽  
...  
Keyword(s):  
Tap Water ◽  
Mammary Carcinogenesis ◽  
Female Rats ◽  
Sprague Dawley ◽  
Short Term ◽  
Antiinflammatory Drugs ◽  
Sprague Dawley Rats ◽  
Term Administration ◽  
Chemopreventive Effect

AbstractChemopreventive effect of non-steroidal antiinflammatory drugs (NSAIDs) in mammary carcinogenesis was reported in several studies. In this study, the effect of a nonselective cyclooxygenase inhibitor diclofenac (DICLO) in the prevention of N-methyl-N-nitrosourea (NMU)-induced mammary carcinogenesis in Sprague-Dawley female rats was evaluated. NMU was administered to animals intraperitoneally in two doses of 50 mg kg−1 b.w. within postnatal days 42-48. In experiment A (short-term administration), DICLO was administrated intramuscularly (5 mg kg−1 b.w.) every other day, starting 3 days before and for subsequent 25 days after first NMU injection. In experiment B (long-term administration), DICLO was administered in tap water (0.01 mg ml−1) continually, starting 7 days before and for subsequent 22 weeks after first NMU dose. The study was terminated 22 weeks after the first dose of NMU in both experiments. After DICLO treatment, tumor frequency per group was reduced in both variants of drug administration: in experiment A by 38% and in experiment B by 39.5%. Moreover, DICLO decreased tumor incidence by 11.5% and delayed tumor latency by 14 days in experiment B. In our preventive-curative experiments DICLO decreased some parameters of NMU-induced rat mammary carcinogenesis, mainly the tumor frequency.

Immunolocalization of ectonucleotidases along the rat nephron

2006 ◽  
Vol 290 (2) ◽  
pp. F550-F560 ◽  
Author(s):  
Renu M. Vekaria ◽  
David G. Shirley ◽  
Jean Sévigny ◽  
Robert J. Unwin
Keyword(s):  
Collecting Duct ◽  
Distal Tubule ◽  
Extracellular Nucleotides ◽  
Thick Ascending Limb ◽  
Sprague Dawley ◽  
Low Level ◽  
Amplification Method ◽  
Sprague Dawley Rats ◽  
Collecting Ducts ◽  
Calbindin D

Evidence is accumulating that extracellular nucleotides act as autocrine/paracrine agents in most tissues, including the kidneys. Several families of surface-located enzymes, collectively known as ectonucleotidases, can degrade nucleotides. Using immunohistochemistry, we have examined the segmental distribution of five ectonucleotidases along the rat nephron. Perfusion-fixed kidneys were obtained from anesthetized male Sprague-Dawley rats. Cryostat sections of cortical and medullary regions were incubated with antibodies specific to the following enzymes: ectonucleoside triphosphate diphosphohydrolase (NTPDase) 1, NTPDase2, NTPDase3, ectonucleotide pyrophosphatase phosphodiesterase 3 (NPP3), and ecto-5′-nucleotidase. Sections were then costained with Phaseolus vulgaris erythroagglutinin (for identification of proximal tubules) and antibodies against Tamm-Horsfall protein (for identification of thick ascending limb), calbindin-D28k (for identification of distal tubule), and aquaporin-2 (for identification of collecting duct). The tyramide signal amplification method was used when the ectonucleotidase and marker antibody were raised in the same species. The glomerulus expressed NTPDase1 and NPP3. The proximal tubule showed prominent expression of NPP3 and ecto-5′-nucleotidase in most, but not all, segments. NTPDase2 and NTPDase3, but not NPP3 or ecto-5′-nucleotidase, were expressed in the thick ascending limb and distal tubule. NTPDase3, with some low-level expression of ecto-5′-nucleotidase, was also found in cortical and outer medullary collecting ducts. Inner medullary collecting ducts displayed low-level staining for NTPDase1, NTPDase2, NTPDase3, and ecto-5′-nucleotidase. We conclude that these ectonucleotidases are differentially expressed along the nephron and may play a key role in activation of purinoceptors by nucleotides and nucleosides.

Independent desensitization of rat renal thick ascending limbs and collecting ducts to ADH

1989 ◽  
Vol 256 (4) ◽  
pp. F656-F663 ◽  
Author(s):  
I. Dublineau ◽  
J. M. Elalouf ◽  
P. Pradelles ◽  
C. de Rouffignac
Keyword(s):  
Collecting Duct ◽  
Synthetic Analogue ◽  
Thick Ascending Limb ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Collecting Ducts ◽  
Normal Rat ◽  
Series Of Experiments ◽  
High Doses

Recent micropuncture studies have demonstrated that administration of high doses of 1-deamino-8-D-arginine vasopressin (dDAVP), a synthetic analogue of vasopressin (AVP), causes desensitization of the thick ascending limb to AVP but may leave unaltered the effect of this hormone on the permeability to water of the collecting duct. In the present experiments, desensitization to AVP was studied by measuring adenosine 3',5'-cyclic monophosphate (cAMP) synthesis in microdissected cortical thick ascending limbs (CTAL) and cortical collecting ducts (CCD) incubated in vitro. Desensitization was induced by intramuscular injections of dDAVP (2 micrograms/day for 3 days). In a first series of experiments, performed on Brattleboro rats lacking circulating AVP, the effects of AVP on cAMP accumulation were reduced by 30% in CTAL of the rats given dDAVP, whereas in CCD no reduction was noted. Desensitization of CTAL was selective for AVP (i.e., homologous), the effects of glucagon being unaltered. In a second series of experiments, performed on Sprague-Dawley rats, a marked (up to 75% 2 h after dDAVP injection), homologous and reversible desensitization of CTAL to AVP was observed. However, here again no desensitization was obtained in CCD, indicating that in the normal rat, administration of 2 micrograms dDAVP also elicited preferential desensitization of CTAL.

Urea transport in isolated thick ascending limbs and collecting ducts from rats

1983 ◽  
Vol 245 (5) ◽  
pp. F634-F639 ◽  
Author(s):  
M. A. Knepper
Keyword(s):  
Thick Ascending Limb ◽  
Sprague Dawley ◽  
Urea Permeability ◽  
Sprague Dawley Rats ◽  
Collecting Ducts ◽  
Outer Stripe ◽  
Passive Absorption ◽  
Urinary Concentrating Ability

The use of pathogen-free rats allows the dissection and in vitro perfusion of several rat nephron segments not previously studied. In the present experiments, net urea fluxes were measured in isolated perfused cortical and medullary thick ascending limbs and cortical collecting ducts from pathogen-free Sprague-Dawley rats. No evidence for active transport of urea was found in either cortical or medullary thick ascending limbs. Permeabilities were calculated from urea fluxes measured with 5 mM urea either in the bath or perfusate and with no urea on the opposite side of the epithelium. Permeability coefficients (cm/s X 10(-5) +/- SE) in different portions of the thick ascending limb were: inner stripe, short-looped nephrons, 0.9 +/- 0.2; inner stripe, long-looped nephrons, 0.6 +/- 0.2 (not significantly different vs. short loops); outer stripe, 1.4 +/- 0.3 (P less than 0.05 vs. inner stripe); and cortical, 1.5 +/- 0.3 (P less than 0.05 vs. inner stripe). The relatively high urea permeability of thick ascending limbs in the outer stripe of the outer medulla and medullary rays is likely to permit substantial passive absorption of urea from these segments in vivo. This will contribute to dilution of the tubule fluid in thick ascending limbs and thus indirectly enhance urinary concentrating ability. In cortical collecting ducts, the urea permeability was relatively low both in the presence of 100 microU/ml arginine vasopressin in the bath (0.5 +/- 0.1 X 10(-5) cm/s) and in its absence (0.4 +/- 0.1). These permeability values are similar to values previously measured in rabbit cortical collecting ducts.

scholarly journals The beneficial effect of long-term supplementation of vitamin C on renal mitochondrial disturbances in streptozotocin-induced diabetic rats

2011 ◽  
Vol 5 (2) ◽  
pp. 277-282
Author(s):  
Mariem Yusuksawad ◽  
Narongsak Chaiyabutr
Keyword(s):  
Vitamin C ◽  
Renal Dysfunction ◽  
Tap Water ◽  
Diabetic Rats ◽  
Mitochondrial Activity ◽  
Sprague Dawley ◽  
Short Term ◽  
Sprague Dawley Rats ◽  
Respiration Control

Abstract Background: Oxidative stress induces renal dysfunction in diabetes, in which renal mitochondrial disturbance was implicated. Vitamin C (VC) supplementation may ameliorate the renal dysfunction in diabetics. However, it is not clear whether VC supplementation is effective for renal mitochondrial disturbances in diabetes. Objective: Investigate whether long-term continuous VC supplementation could ameliorate the renal mitochondrial disturbances in streptozotocin (STZ)-induced diabetic rats. Methods: Thirty-five male Sprague-Dawley rats were used, and diabetes was induced by an injection of STZ. The rats were divided into three groups: control rats (CON), STZ-induced diabetic rats (STZ), and diabetic rats supplemented by vitamin C (STZ-VC). The CON and STZ rats were given tap water, while STZ-VC rats received VC (1 g/L) every day for eight, 24 and 52 weeks. The kidney was isolated and homogenized. Oxygen comsumption (Vo2) was measured in mitochondria homogenate using an oxygen consumption monitor. Based on Vo2 tracings, the respiration control index (RCI) and P/O ratio (= ADP/ O ratio) were measured at week 8, 24 and 52. Results: At week eight, using either glutamate plus malate (for site I) or succinate (for site II) as substrates, both RCI and P/O ratio were not significantly different among three groups. The P/O ratio in STZ and STZ-VC rats increased from eight to 52 weeks after VC supplementation. At week 24, the P/O ratio at site II was normalized in STZ-VC rat. The increased P/O ratio (only site I) and the increased RCI (only site II) of STZ-VC rats were slower than those of STZ rats. Conclusion: Short-term VC supplementation might not influence the renal mitochondrial activity. The long-term VC supplementation could ameliorate the mitochondrial disturbances induced in STZ-induced diabetic rats.

Long-term exposure of Sprague Dawley rats to 20 kHz triangular magnetic fields

2006 ◽  
Vol 82 (4) ◽  
pp. 285-291 ◽  
Author(s):  
H. J. Lee ◽  
S. H. Kim ◽  
S. Y. Choi ◽  
Y. M. Gimm ◽  
J. K. Pack ◽  
...  
Keyword(s):  
Magnetic Fields ◽  
Sprague Dawley ◽  
Sprague Dawley Rats

scholarly journals Transient Neonatal Cryptosporidium parvum Infection Triggers Long-Term Jejunal Hypersensitivity to Distension in Immunocompetent Rats

2006 ◽  
Vol 74 (7) ◽  
pp. 4387-4389 ◽  
Author(s):  
Rachel Marion ◽  
Asiya Baishanbo ◽  
Gilles Gargala ◽  
Arnaud François ◽  
Philippe Ducrotté ◽  
...  
Keyword(s):  
Cryptosporidium Parvum ◽  
Myeloperoxidase Activity ◽  
Sprague Dawley ◽  
Depressor Response ◽  
Sprague Dawley Rats

ABSTRACT In 5-day-old immunocompetent Sprague-Dawley rats infected with either 102 or 105 Cryptosporidium parvum oocysts, transient infection resulted 120 days later in increased cardiovascular depressor response to jejunal distension and jejunal myeloperoxidase activity (P < 0.05). Nitazoxanide treatment normalized jejunal sensitivity (P < 0.001) but not myeloperoxidase levels (P > 0.05). Data warrant further evaluation of the role of early cryptosporidiosis in the development of chronic inflammatory gut conditions.

Thick ascending limb claudins are altered to increase calciuria and magnesiuria in metabolic acidosis

2021 ◽  
Author(s):  
Il Hwan Oh ◽  
Chor Ho Jo ◽  
Sua Kim ◽  
Sungsin Jo ◽  
Sungjin Chung ◽  
...  
Keyword(s):  
Metabolic Acidosis ◽  
Immunofluorescence Microscopy ◽  
Urinary Calcium ◽  
Receptor Protein ◽  
Thick Ascending Limb ◽  
Sprague Dawley ◽  
Calcium Sensing Receptor ◽  
Calcium Sensing ◽  
Sprague Dawley Rats ◽  
Calcium And Magnesium

Urinary calcium and magnesium wasting is a characteristic feature of metabolic acidosis, and this study focused on the role of the thick ascending limb of Henle's loop in metabolic acidosis-induced hypercalciuria and hypermagnesiuria because thick ascending limb is an important site of paracellular calcium and magnesium reabsorption. Male Sprague-Dawley rats were used to determine the effects of acid loading (by adding NH4Cl 7.2 mmol/220 g BW/d to food slurry for 7 days) on renal expression of claudins and then to evaluate whether the results were reversed by antagonizing calcium-sensing receptor (using NPS-2143). At the end of each animal experiment, the kidneys were harvested for immunoblotting, immunofluorescence microscopy and qPCR analysis of claudins and the calcium-sensing receptor. As expected, NH4Cl loading lowered urinary pH and increased excretion of urinary calcium and magnesium. In NH4Cl-loaded rats, renal protein and mRNA expression of claudin-16, and claudin-19 decreased compared with controls. However, claudin-14 protein and mRNA increased in NH4Cl-loaded rats. Consistently, the calcium-sensing receptor protein and mRNA were upregulated in NH4Cl-loaded rats. All these changes were reversed by NPS-2143 coadministration and were confirmed using immunofluorescence microscopy. Hypercalciuria and hypermagnesiuria in NH4Cl-loaded rats were significantly ameliorated by NPS-2143 coadministration as well. We conclude that in metabolic acidosis, claudin-16 and claudin-19 in the thick ascending limb are downregulated to produce hypercalciuria and hypermagnesiuria via the calcium-sensing receptor.

Sign in / Sign up

Export Citation Format

Share Document