scholarly journals Amiloride: A review

2020 ◽  
Vol 21 (4) ◽  
pp. 147032032097589
Author(s):  
Qianhui Sun ◽  
Peter Sever
Keyword(s):  
Potential Role ◽  
Hepatic Cirrhosis ◽  
Collecting Duct ◽  
Dose Range ◽  
Distal Tubule ◽  
Metabolic Effects ◽  
Epithelial Sodium Channels ◽  
Medical Research Council Trial ◽  
Number Of Patients ◽  
Coronary Events

Amiloride is a potassium retaining diuretic and natriuretic which acts by reversibly blocking luminal epithelial sodium channels (ENaCs) in the late distal tubule and collecting duct. Amiloride is indicated in oedematous states, and for potassium conservation adjunctive to thiazide or loop diuretics for hypertension, congestive heart failure and hepatic cirrhosis with ascites. Historical studies on its use in hypertension were poorly controlled and there is insufficient data on dose-response. It is clearly highly effective in combination with thiazide diuretics where it counteracts the adverse metabolic effects of the thiazides and its use in the Medical Research Council Trial of Older Hypertensive Patients, demonstrated convincing outcome benefits on stroke and coronary events. Recently it has been shown to be as effective as spironolactone in resistant hypertension but there is a real need to establish its potential role in the much larger number of patients with mild to moderate hypertension in whom there is a paucity of information with amiloride particularly across an extended dose range.

Adaptation of distal tubule and collecting duct to increased Na delivery. II. Na+ and K+ transport

1988 ◽  
Vol 255 (6) ◽  
pp. F1269-F1275 ◽  
Author(s):  
B. A. Stanton ◽  
B. Kaissling
Keyword(s):  
Tap Water ◽  
Collecting Duct ◽  
Basolateral Membrane ◽  
Extracellular Fluid ◽  
Distal Tubule ◽  
Sodium Absorption ◽  
Transport Capacity ◽  
Volume Depletion ◽  
Osmotic Minipump ◽  
Sodium Uptake

This study was conducted to determine whether a chronic increase in sodium delivery to, and sodium uptake by, the distal tubule stimulates the transport capacity of this tubular segment. To increase the rate of sodium delivery to the distal tubule, furosemide (12 mg/day) was administered continuously to rats by osmotic minipump for 6 days. Volume depletion was prevented by giving the animals a drinking solution containing 0.8% NaCl and 0.1% KCl. Control animals were given vehicle (0.9% NaCl) by osmotic minipump and tap water to drink. All animals were adrenalectomized and given replacement doses of aldosterone (0.5 microgram.100 g-1.day-1) and dexamethasone (1.2 microgram.100 g-1.day-1) to eliminate changes in adrenal corticosteroid levels. Furosemide was withdrawn 12 h before sodium and potassium transport rates were measured in distal tubules by in vivo microperfusion. We found that increased sodium uptake dramatically enhanced the transport capacity of the distal tubule. Sodium absorption rose from 71.7 to 316.7 pmol.min-1.mm-1, and potassium secretion increased from 30.7 to 73.7 pmol.min-1.mm-1. This response was accompanied by an increase in cell and mitochondrial volume and by proliferation of the basolateral membrane of distal convoluted cells, connecting tubule cells, and principal cells in the distal tubule. We conclude that a chronic increase in sodium uptake by the distal tubule, independent of alterations in extracellular fluid volume and aldosterone levels, stimulates the transport capacity of this nephron segment in part by inducing specific alterations in cell ultrastructure.

Cadmium is more toxic to LLC-PK1cells than to MDCK cells acting on the cadherin-catenin complex

1998 ◽  
Vol 275 (1) ◽  
pp. F143-F153 ◽  
Author(s):  
L. B. Zimmerhackl ◽  
F. Momm ◽  
G. Wiegele ◽  
M. Brandis
Keyword(s):  
Mdck Cells ◽  
Morphological Changes ◽  
Collecting Duct ◽  
Cadmium Toxicity ◽  
Distal Tubule ◽  
Insoluble Fraction ◽  
Atp Depletion ◽  
Rhodamine Phalloidin ◽  
Apical Side ◽  
E Cadherin

Cadmium toxicity to renal cells was investigated in Madin-Darby canine kidney (MDCK) and LLC-PK1cells as models of the distal tubule/collecting duct and proximal tubule, respectively. Cells were grown on two-compartment filters and exposed to 0.1–50 μM Cd2+. In MDCK cells, Cd2+was more toxic from the basolateral than from the apical side and dependent on the extracellular Ca2+concentration. Toxicity was evident within 24 h, as shown by a decrease in transepithelial resistance (TER), reduced proliferation (bromodeoxyuridine incorporation), reduction in ATP concentration, and morphological changes. On confocal microscopy, E-cadherin and α-catenin staining patterns indicated interference with the cadherin-catenin complex. LLC-PK1cells showed a similar toxicity pattern, which was evident at lower Cd2+concentrations. An increase of E-cadherin and α-catenin molecules in the Triton X-100-insoluble fraction was detectable at high Cd2+concentrations in LLC-PK1cells but not in MDCK cells. Lactate dehydrogenase release indicated membrane leakage in LLC-PK1cells. Rhodamine-phalloidin staining, a probe for F-actin filaments, demonstrated alterations of the actin cytoskeleton in both cell lines. In conclusion, cadmium caused ATP depletion and interfered with the cadherin-catenin complex and probably the tight junctions changing renal cell morphology and function.

Abnormal postpartum renal development and cystogenesis in the bcl-2 (-/-) mouse

1996 ◽  
Vol 271 (1) ◽  
pp. F184-F193 ◽  
Author(s):  
C. M. Sorenson ◽  
B. J. Padanilam ◽  
M. R. Hammerman
Keyword(s):  
Cellular Proliferation ◽  
Kidney Development ◽  
Apoptotic Cell ◽  
Collecting Duct ◽  
Distal Tubule ◽  
Renal Development ◽  
Thick Ascending Limb ◽  
Renal Hypoplasia ◽  
Cellular Origin ◽  
Bax Protein

Mice deficient for B cell leukemia/lymphoma gene 2 [bcl-2(-/-) mice] manifest congenital renal hypoplasia and develop multicystic kidney disease and renal failure postnatally. To characterize postpartum renal development, to identify the cellular origin of the cysts, and to provide insight into the role that bcl-2 deficiency plays in the cystogenic process, we examined the morphology of kidneys from bcl-2 (-/-) mice and wild-type littermates [bcl-2 (+/+)] from birth (P0) to postpartum day 28 (P28), determined whether abnormalities of cellular proliferation and apoptosis accompany cyst development, and characterized expression of the bcl-2-related protein, bax. Between P0 and P7, kidneys from bcl-2 (-/-) and bcl-2 (+/+) mice undergo a comparable increase in weight and have similar histological appearances. However, during the next 2 wk of life, weight gain in kidneys from bcl-2 (-/-) mice is reduced compared with that in kidneys from bcl-2 (+/+) animals, and cysts develop in tubules with staining characteristics of proximal tubule, distal tubule/medullary thick ascending limb of Henle's loop, and collecting duct. Unaffected glomeruli and proximal tubules in kidneys of bcl-2 (-/-) mice undergo compensatory growth. Cystogenesis is accompanied by enhanced incorporation of 5-bromo-2'-deoxyuridine in cells within cortex and medulla and apoptosis of cells within cysts and in the renal interstitium. Bax protein is expressed in the distal tubule in kidneys of bcl-2 (+/+) and bcl-2 (-/-) mice and in some, but not all cysts. We conclude that abnormal regulation of DNA synthesis and apoptosis accompany cystogenesis in bcl-2 (-/-) mice during postpartum kidney development. Continued expression of bax could enhance apoptotic cell death.0

scholarly journals Differential Expression Patterns of Claudins, Tight Junction Membrane Proteins, in Mouse Nephron Segments

2002 ◽  
Vol 13 (4) ◽  
pp. 875-886 ◽  
Author(s):  
Yumiko Kiuchi-Saishin ◽  
Shimpei Gotoh ◽  
Mikio Furuse ◽  
Akiko Takasuga ◽  
Yasuo Tano ◽  
...  
Keyword(s):  
Membrane Proteins ◽  
Tight Junction ◽  
Polyclonal Antibodies ◽  
Collecting Duct ◽  
Expression Patterns ◽  
Distal Tubule ◽  
Northern Blotting ◽  
Thick Ascending Limb ◽  
Specific Expression ◽  
Nephron Segments

ABSTRACT. As the first step in understanding the physiologic functions of claudins (tight junction integral membrane proteins) in nephrons, the expression of claudin-1 to -16 in mouse kidneys was examined by Northern blotting. Among these claudins, only claudin-6, -9, -13, and -14 were not detectable. Claudin-5 and -15 were detected only in endothelial cells. Polyclonal antibodies specific for claudin-7 and -12 were not available. Therefore, the distributions of claudin-1, -2, -3, -4, -8, -10, -11, and -16 in nephron segments were examined with immunofluorescence microscopy. For identification of individual segments, antibodies specific for segment markers were used. Immunofluorescence microscopic analyses of serial frozen sections of mouse kidneys with polyclonal antibodies for claudins and segment markers revealed that claudins demonstrated very complicated, segment-specific, expression patterns in nephrons, i.e., claudin-1 and -2 in Bowman’s capsule, claudin-2, -10, and -11 in the proximal tubule, claudin-2 in the thin descending limb of Henle, claudin-3, -4, and -8 in the thin ascending limb of Henle, claudin-3, -10, -11, and -16 in the thick ascending limb of Henle, claudin-3 and -8 in the distal tubule, and claudin-3, -4, and -8 in the collecting duct. These segment-specific expression patterns of claudins are discussed, with special reference to the physiologic functions of tight junctions in nephrons.

The Dose Determines the Stimulation (and Poison): Development of A Chemical Hormesis Database

1997 ◽  
Vol 16 (6) ◽  
pp. 545-559 ◽  
Author(s):  
Edward J. Calabrese ◽  
Linda A. Baldwin
Keyword(s):  
A Priori ◽  
Dose Range ◽  
Evaluation Criteria ◽  
Metabolic Effects ◽  
Growth Responses ◽  
Wide Range ◽  
Order Of Magnitude ◽  
Real Phenomenon ◽  
Effect Level ◽  
Taxonomic Groups

A comprehensive effort was undertaken to identify articles demonstrating chemical hormesis. Nearly 4000 potentially relevant articles were retrieved from preliminary computer searches utilizing various keyword descriptors and extensive cross-referencing. A priori evaluation criteria were established including study design features (e.g., number of doses, dose range), statistical analysis, and reproducibility of results. Evidence of chemical hormesis was judged to have occurred in approximately 350 of the 4000 studies evaluated. Chemical hormesis was observed in a wide range of taxonomic groups and involved agents representing highly diverse chemical classes, many of potential environmental relevance. Numerous biologic endpoints were assessed, with growth responses the most prevalent, followed by metabolic effects, longevity, reproductive responses, and survival. Hormetic responses were generally observed to be of limited magnitude with the average low-dose maximum stimulation approximately 50% greater than controls. The hormetic dose-response range was generally limited to about one order of magnitude with the upper end of the hormetic curve approaching the estimated no-observed-effect level (NOEL) for the particular endpoint. Based on the evaluation criteria, high to moderate evidence of hormesis was observed in studies comprised of ≥ doses with <3 doses in the hormetic zone. The present analysis suggests that chem ical hormesis is a reproducible and generalizable biologic phenomenon. Over the last decade advances have been made providing mechanistic insight helpful in explaining the phenomenon of chemical hormesis in multiple biologic systems with various endpoints. The reason for the uncertainty surrounding the existence of hormesis as a “real phenomenon” is believed to be the result of its relatively infrequent observation in the literature due to experimental design considerations, especially with respect to the number of doses, range of doses, and endpoint selection.

Potassium transport in the distal tubule and collecting duct of the rat

1975 ◽  
Vol 229 (5) ◽  
pp. 1403-1409 ◽  
Author(s):  
HJ Reineck ◽  
RW Osgood ◽  
TF Ferris ◽  
JH Stein
Keyword(s):  
Flow Rate ◽  
Collecting Duct ◽  
Distal Tubule ◽  
Potassium Transport ◽  
Distal Convoluted Tubule ◽  
Potassium Excretion ◽  
Flow Rates ◽  
Urinary Potassium ◽  
Potassium Secretion ◽  
Tubular Flow

Because of recent conflicting results, micropuncture studies were performed to clarify the respective role of the distal convoluted tubule and collecting duct in the regulation of urinary potassium excretion. Five groups of Sprague-Dawley rats were studied: group I, hydropenia (n = 10); group II, Ringer loading (n = 7); group III, acute KC1 loading (n = 6); group IV, mannitol diuresis (n = 6); group V, KC1 infusion during mannitol diuresis (n = 7). Early and late distal tubules were identified with intravenous injections of lissamine green. In each animal net secretion of potassium occurred along the distal convoluted tubule, and a direct relationship between distal tubular flow rate and potassium secretion was observed. The magnitude of potassium secretion at high distal tubular flow rates was dependent on the model studied. Potassium transport beyond the distal tubule was evaluated by comparing end distal potassium delivery and fractional potassium excretion. At low urinary flow rates net reabsorption was observed, whereas at higher flow rates no net transport occurred. Thus, flow rate along the collecting duct may be a major determinant of urinary potassium excretion.

Heat stress protein-associated cytoprotection of inner medullary collecting duct cells from rat kidney

1993 ◽  
Vol 265 (3) ◽  
pp. F333-F341 ◽  
Author(s):  
S. C. Borkan ◽  
A. Emami ◽  
J. H. Schwartz
Keyword(s):  
Heat Stress ◽  
Thermal Injury ◽  
Collecting Duct ◽  
Rat Kidney ◽  
Metabolic Effects ◽  
Lactate Dehydrogenase Activity ◽  
Inner Medullary Collecting Duct ◽  
Duct Cells ◽  
Collecting Duct Cells ◽  
Medullary Collecting Duct

Although heat stress proteins (HSPs) mediate thermotolerance, the cellular targets of thermal injury and mechanisms of acquired cytoprotection are unknown. To describe the metabolic effects of hyperthermia and the potential mechanisms of thermotolerance, the following were measured in inner medullary collecting duct cells after a 43 degrees C and/or a 50 degrees C thermal insult: 1) state III mitochondrial respiration (SIII MR), 2) glycolytic rate, 3) lactate dehydrogenase activity, 4) membrane permeability, and 5) HSP 72 content. Compared with controls incubated at 37 degrees C, cells heated to 50 degrees C showed a 30 and 50% reduction in glycolysis and SIII MR, respectively. After heating to 50 degrees C, the cell membrane remained intact and immunoreactive HSP 72 was not detected. In contrast, heating to 43 degrees C induced accumulation of HSP 72 and transiently increased both SIII MR and glycolysis. In addition, prior exposure to 43 degrees C completely prevented the fall in SIII MR and glycolysis anticipated with a subsequent 50 degrees C insult. Cytoprotection gradually diminished over several days and correlated with the disappearance of HSP 72. Preservation of oxidative and anaerobic metabolism associated with HSPs may be important in developing resistance to thermal injury.

scholarly journals AMP-Activated Protein Kinase (AMPK)-Dependent Regulation of Renal Transport

2018 ◽  
Vol 19 (11) ◽  
pp. 3481 ◽  
Author(s):  
Philipp Glosse ◽  
Michael Föller
Keyword(s):  
Membrane Transport ◽  
Active Transport ◽  
Collecting Duct ◽  
Distal Tubule ◽  
Transport Processes ◽  
Acid Oxidation ◽  
Serine Threonine Kinase ◽  
Energy Deficiency ◽  
Energy Consuming ◽  
Amp Activated Protein Kinase

AMP-activated kinase (AMPK) is a serine/threonine kinase that is expressed in most cells and activated by a high cellular AMP/ATP ratio (indicating energy deficiency) or by Ca2+. In general, AMPK turns on energy-generating pathways (e.g., glucose uptake, glycolysis, fatty acid oxidation) and stops energy-consuming processes (e.g., lipogenesis, glycogenesis), thereby helping cells survive low energy states. The functional element of the kidney, the nephron, consists of the glomerulus, where the primary urine is filtered, and the proximal tubule, Henle’s loop, the distal tubule, and the collecting duct. In the tubular system of the kidney, the composition of primary urine is modified by the reabsorption and secretion of ions and molecules to yield final excreted urine. The underlying membrane transport processes are mainly energy-consuming (active transport) and in some cases passive. Since active transport accounts for a large part of the cell’s ATP demands, it is an important target for AMPK. Here, we review the AMPK-dependent regulation of membrane transport along nephron segments and discuss physiological and pathophysiological implications.

scholarly journals Metabolic Effects of Bile Acids: Potential Role in Bariatric Surgery

2019 ◽  
Vol 8 (2) ◽  
pp. 235-246 ◽  
Author(s):  
Charles R. Flynn ◽  
Vance L. Albaugh ◽  
Naji N. Abumrad
Keyword(s):  
Bariatric Surgery ◽  
Bile Acids ◽  
Potential Role ◽  
Metabolic Effects

Effects of aldosterone on potassium recycling in the kidney of adrenalectomized rats

1985 ◽  
Vol 248 (2) ◽  
pp. F219-F227 ◽  
Author(s):  
E. Higashihara ◽  
J. P. Kokko
Keyword(s):  
Wistar Rats ◽  
Collecting Duct ◽  
Distal Tubule ◽  
Feedback System ◽  
Blood Levels ◽  
Segmental Analysis ◽  
Urinary Potassium ◽  
Papillary Collecting Duct ◽  
Potassium Secretion ◽  
Potassium Recycling

Recent studies have suggested that potassium, like urea, undergoes medullary recycling. The present cortical and papillary micropuncture studies were designed to confirm the existence of medullary potassium recycling and to determine whether acute infusions of aldosterone affected this phenomenon. Thus, nephron segmental analysis of potassium and sodium transport was conducted in adrenalectomized Munich-Wistar rats and similarly prepared rats that received aldosterone acutely to achieve physiological blood levels. The clearance results demonstrated that aldosterone has an acute antinatriuretic and a kaliuretic effect, whereas the micropuncture studies demonstrated that 1) aldosterone increases potassium secretion between early and late distal tubule punctures; 2) aldosterone causes an increase in delivery of potassium to the papillary collecting duct; 3) aldosterone does not increase potassium secretion across the papillary collecting duct; and 4) aldosterone significantly increases medullary potassium recycling as evidenced by increased quantities of potassium present at the bend of the loop of Henle in response to aldosterone infusions. Thus, the studies confirm the existence of potassium recycling and suggest that this phenomenon is a feedback system that, in part, regulates urinary potassium excretion.

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