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At least 19 recordsLinked to original sources

PubMed1986

Effect of cyclosporine A on renal electrolyte transport: whole kidney and Henle loop study.

We investigated whole kidney function and electrolyte transport in the loop of Henle of surface nephrons using micropuncture in rats pretreated for 5-7 days with cyclosporine A (CSA, 15 mg/kg). We also studied whether the kidney was able to increase K+ excretion acutely after a period of acute i.v. KCl loading (37 mumol/min.kg body weight). For Henle loop studies we microperfused the late proximal tubule downstream from an immobile wax block at two perfusion rates (15 and 40 nl/min). The fluid at the beginning distal tubule was collected and analyzed for inulin, Na+, K+, Cl-, Ca++, and Mg++. Plasma levels of CSA in our model ranged from 254 and 971 ng/ml and showed no relation to the obtained measurements. The pretreatment with CSA did not significantly change whole kidney or Henle loop electrolyte transport compared to drug free controls. Also, the CSA-pretreated rats were able to excrete an acute KCl load although this was at the expense of a marginally higher plasma K+ concentration and also a smaller urine flow increase during KCl loading. Thus CSA-pretreated rats showed only a mildly impaired response to KCl challenge in the absence of GFR impairment.

Animals↗

PubMed1976

The function of (Na+, K+)-ATPase in the thick ascending limb of Henles loop.

The content and the properties of (Na+, K+)-ATPase in the thick ascending limb of the loop of Henle (TAL) are related to the rate and the characteristics of the transport of NaCl which has been measured in the isolated perfused cortical portion of the TAL by Burg and Green (Am. J. Physiol, 224, 659, 1973) and in the medullary portion of the TAL by Rocha and Kokko (J. Clin. Invest. 52, 612, 1973). It is concluded that the ouabain-sensitive, active transport of NaCl across the epithelium consists of primary active transport of Na and secondary active transport of Cl and that it is driven by the sodium pump or (Na+, K+)-ATPase.

Adenosine Triphosphatases↗

PubMed1987

Sodium reabsorption by the Henle loop in humans.

In a previous study, we described a new method [3] to measure Na reabsorption by each segment of the human nephron independently. Reabsorption was expressed as equivalent volumes of solute-free water (CH2O) generated by the loop of Henle (CH2O-HL) and by the distal tubule (CH2O-DT), and dissipated by back diffusion (BD) across collecting ducts (CH2O-BD). These data were obtained during maximal water diuresis (MWD). The present study was undertaken to calculate CH2O-HL by experiments performed during maximal antidiuresis (MA). For this purpose, a new theoretical approach was devised, described by algebraic equations which allowed calculations of segmental transport during MA alone, where only CH2O-HL could be calculated independently. The study was performed on 14 normal volunteers who were studied twice by clearance measurements, firstly during MWD and again during MA. In each experiment, clearance periods were performed during baseline conditions and during the administration of furosemide (0.7 mg/kg bolus injection followed by 0.06 mg/kg/min maintenance infusion). From the values measured during either condition, segmental reabsorption was calculated. During MWD, CH2O-HL averaged 19.4 + 10.4, during MA 20.4 + 8.0 ml/min/GFR X 100; p greater than 0.05. The paired measurements were significantly correlated (r = 0.80; p less than 0.01). These data demonstrate that CH2O-HL obtained with the original theory is a reproducible result that can be confirmed with independent measurements obtained during different experimental conditions. Thus, measurements of segmental Na transport in the human nephron are feasible and can contribute important informations on disease states.

Absorption↗

PubMed1988

Effect of inhibitors of prostaglandin synthesis on the furosemide action in the loop Henle of rat kidney.

Inhibitors of prostaglandin synthesis such as indomethacin and meclofenamate may attenuate the diuretic response to furosemide. The purpose of the present study was to clarify whether an inhibition of furosemide's action in the loop of Henle is involved in this interaction. In a first set of experiments, the effect of indomethacin and meclofenamate on the diuretic response to furosemide was re-evaluated in anaesthetized rats. Single loops of Henle of rat kidneys were perfused in vivo in a second group of rats. Furosemide was added to the perfusion fluid and the effect of indomethacin (5 mg/kg i.v.) and meclofenamate (5 mg/kg i.v.) on furosemide's action in the loops was tested. In the absence of furosemide, indomethacin and meclofenamate did not significantly affect urine flow and sodium chloride excretion, or the loop's sodium and chloride reabsorption. Both prostaglandin inhibitors, however, significantly attenuated the diuretic effect of furosemide (1 mg/kg i.v.) and the inhibitory action of the diuretic, at a concentration of 10(-4) M, on the loop's sodium and chloride transport. The results identify the loop of Henle as a tubular site of interaction between furosemide and prostaglandin inhibitors. The interaction may be related to a furosemide-induced stimulation of renal prostaglandins.

Animals↗

PubMed1988

Inhibition of active NaCl reabsorption in the thick ascending limb of the loop of Henle by torasemide.

The new diuretic torasemide (1-isopropyl-3- ([4-(3-methyl-phenylamino)pyridine]-3-sulfonyl)urea) was tested in isolated in vitro perfused cortical thick ascending limbs of Henle loops of rabbit kidney. The equivalent short circuit current (Isc) corresponding in this nephron segment to the rate of secondarily active Cl-reabsorption was measured continuously. Torasemide led to a rapid and reversible inhibition of Isc when added to the luminal perfusate. The IC50 for this effect was 3 x 10(-7) mol/l. A similar effect was also exerted by torasemide addition to the peritubular bath. However, 100 times larger doses were needed. The data are compatible with the view that torasemide interacts with both, the Na+2Cl-K+ carrier, localized in the luminal membrane, and, at higher concentrations, with the chloride channels present in the basolateral membrane of this nephron segment. Under normal conditions, and in the intact kidney, the former effect, i.e. interference with the Na+2Cl-K+ carrier will be the dominant action of this drug.

Absorption↗

PubMed1986

[Diuretics].

Microaspiration techniques and clearance studies have shown that reabsorption of filtered sodium approximates 65% in the proximal tubule, 25 to 30% in the ascending limb of the loop of Henle and 5 to 10% in the dilution segment. Reabsorption in the Henle loop is of special significance as it governs the process of dilution-concentration of urine. Moreover, inhibition of sodium reabsorption in the loop of Henle necessarily produces a substantial loss of sodium since only a fairly small fraction of urinary sodium is reabsorbed beyond the Henle loop (dilution segment, distal tubule). Excretion of water and electrolytes is regulated by humoral factors, such as the renin-angiotensin-aldosterone system, some prostaglandins and certain kinins. Factors that promote excretion of sodium, produced in particular by the myocardium, have recently been demonstrated. The correlation between blood pressure and salt has been substantiated by many findings. Diuretics are commonly used to treat high blood pressure as well as edema. Recent evidence indicates that sodium transport is altered in idiopathic hypertension, at least in red blood cells. Clinical trials of diuretics are designed to localize the drug's action and quantify its saluretic activity (evaluation of potency and effectiveness--single doses, sustained treatment). Furthermore, the minimal efficient antihypertensive dosage should be determined. Diuretics can be divided into two groups according to whether they produce an increase or decrease in serum potassium. Diuretics that are capable of producing hypokalemia belong to two main families. One consists of the Henle loop diuretics that interfere with the mechanisms of dilution-concentration of urine. Action of these drugs is potent and short-lived. For instance, following a single dose of furosemide, excretion of sodium can reach 25-30% of filtered sodium; renal blood flow increases; CH2O and TCH2O decrease. With furosemide, induction of diuresis is rapid (within a few minutes after IV injection and 20 mn after oral ingestion); elimination half-life is 50 mn; absolute bioavailability is 50-70%; 95% of the drug is bound to plasma proteins; elimination is mainly through the kidneys. Other Henle loop diuretics include ethacrynic acid, whose elimination half-life is less than one hour; bumetanide, which is 40 times more potent than furosemide; muzolimine, whose action is more lasting despite the fact that only 65% of the drug is bound to plasma proteins; and ozolinone, which has a saliuretic action comparable to that of furosemide and in addition exerts a direct vasodilating effect.(ABSTRACT TRUNCATED AT 400 WORDS)

Acid-Base Equilibrium↗

PubMed1970

Fluid reabsorption in Henle's loop and urinary excretion of sodium and water in normal rats and rats with chronic hypertension.

The function of the short loops of Henle was investigated by micropuncture technique in normal rats, in rats with spontaneous hypertension, and in the untouched kidney of rats with experimental renal hypertension. All animals received a standard infusion of 1.2 ml of isotonic saline per hr. With increasing arterial blood pressure (range from 90 to 220 mm Hg), a continuous decrease in transit time of Lissamine green through Henle's loop from 32 to 10 sec was observed. Fractional water reabsorption along the loop declined progressively from 26 to 10%, and fractional sodium reabsorption decreased from 40 to 36% of the filtered load. The fluid volume in Henle's loop calculated from transit time and mean flow rate also decreased with increasing blood pressure. There was no change in superficial single nephron filtration rate but there was a slight increase in total glomerular filtration rate (GFR). Sodium and water reabsorption in the proximal tubule remained unchanged. Urine flow rate, sodium excretion, osmolar clearance, and negative free water clearance increased with increasing blood pressure. The osmolal urine to plasma (U/P) ratio declined but did not fall below a value of 1.5. It is concluded that the increase in sodium and water excretion with chronic elevation of arterial blood pressure is caused by a decrease of sodium and water reabsorption along the loop of Henle, presumably as a consequence of increased medullary blood pressure.

Animals↗

PubMed1990

Amino acid transport: microinfusion and micropuncture of Henle's loops and vasa recta.

Amino acids appear to be reabsorbed distal to the tips of loops of Henle and may be recycled between loops and vasa recta in rat papilla. These possibilities were examined further by microinfusion and micropuncture of loops of Henle and vasa recta. To obtain information on the specificity of amino acid transport distal to the tips of the loops, ascending limbs were continuously microinfused with radioactively labeled L- and D-alanine, L-glutamate, taurine, and mannitol. About 30% of the L- and D-alanine and L-glutamate but none of the taurine or mannitol appeared to be reabsorbed. These results suggest that an acidic and a neutral amino acid are reabsorbed to a similar extent, that reabsorption is not stereospecific, but that it does not occur indiscriminately for all amino acids or for all molecules of similar size. Continuous microinfusion of ascending vasa recta with radioactively labeled L- and D-alanine suggests that amino acids may be able to move from vasa recta into tubules (apparently loops of Henle) without first entering the systemic circulation. However, micropuncture measurements of concentrations of endogenous amino acids in thin ascending limbs and adjacent descending vasa recta do not demonstrate a gradient for passive movement out of loops.

Alanine↗

PubMed1985

Effect of acute potassium load on reabsorption in Henle's loop in chronic renal failure in the rat.

To determine the effect of an acute load of potassium on potassium reabsorption by the loop of Henle in chronic renal failure, the right kidney was removed and branches of the left renal artery were ligated in 17 rats. One week later and after 2 days of a potassium-free diet, rats were studied before (period 1) and after (period 2) acute loads of potassium chloride (KCl group), equimolar sodium chloride (NaCl group) or no solute (time control). The KCl load increased urinary potassium excretion to a greater extent (from 5 to 50%, P less than 0.005) than in NaCl (14 to 27%) or time control (9 to 14%), and caused as great a diuresis and natriuresis as did NaCl. Fractional delivery of water, sodium, and potassium to the end-proximal tubule increased similarly in the NaCl and KCl groups and slightly less so in the time control group in period 2. The major finding was a striking increase in potassium delivery to the beginning of the distal tubule (from 17 to 37%) in period 2 which was substantially greater than in the combined control groups (13 to 19%, P less than 0.025) and was equivalent to three-quarters of urinary potassium excretion. This was the consequence of an increase in the filtered load of potassium, an increase in absolute delivery of potassium from the proximal tubule (P less than 0.005), and a decrease in fractional potassium reabsorption by the loop of Henle from 64 to 48%, versus 72 to 69% in the control groups (P less than 0.01). These results suggest that the proximal tubule and, in particular, Henle's loop play a role in excreting an acute potassium load in chronic renal failure.

Animals↗

PubMed1978

Examination of transport equations pertaining to permeable elastic tubules such as Henle's loop.

The transport equations applicable to loops of Henle and similar elastic permeable tubules were re-examined to assess the effect of radial transport resistance in the lumen and tubule geometry on solute transport. Active transport at the wall as well as external gradients equivalent to a 2--1,000-fold concentration increase per centimeter of distance were considered. Wall permeabilities and active transport constants were varied up to 2 . 10(-2) cm/s. It is shown that for conditions applicable to the loop of Henle, resistance to radial solute transfer in the lumen is negligible, both for passive and active transmural transport with concomitant water flux, and that axial dispersion further reduces that resistance. These conclusions apply equally to conical and elliptical geometries likely to arise in loop operation. The validity of Poiseuille's equation for these geometries is discussed. Ii is concluded that the one-dimensional transport equations are a valid representation of loop operation.

Biological Transport, Active↗

PubMed1983

Cellular mechanism of the action of loop diuretics on the thick ascending limb of Henle's loop.

During the passed few years the cellular mechanisms responsible for the NaCl reabsorption in the thick ascending limb of the Henle loop of mammalian nephron and of the early distal tubule of amphibian kidney have been extensively studied. From these studies a new type of secondarily active transport mechanism, i.e. the Na+--2Cl- --K+ symport has emerged. Meanwhile it has been recognized that this system is also present in many other epithelia. All these epithelia share in common that they are sensitive to the so called loop diuretics. The present article summarizes our current knowledge of how the loop diuretics, by reversible interaction with the above cotransport system, inhibit the NaCl reabsorption in the thick ascending limb of Henle's loop. It is shown that these drugs transfer the thick ascending limb cell to a state in which not only transepithelial NaCl reabsorption ceases but in which also very little energy is consumed since then K+ and Cl- "relax" to passive distribution across both cell membranes and Na+ entry into the cell is blocked.

Absorption↗

PubMed1979

Effects of lumen volume transit time and pressure on loop of Henle function.

Experiments on Henle's loops were designed to demonstrate the relationships of absorption to distal pressure, transit time, and luminal diameter. Loops of superficial nephrons in hydropenic rats, isolated from the rest of the nephron by oil or solid paraffin blocks, were microperfused at 13.6--20 nl/min. Two samples of fluid were collected from the early distal tubule--one with suction in order to lower distal pressure and reduce luminal volume, the other without suction so that the lumen was distended. Transit times were 30 +/- 2 s without and 19 +/- 2 s with suction. Proximal tubule pressure and perfusion rate were not altered by collection with suction. Absolute absorption, however, descreased from 10.6 +/- 0.4 to 8.4 +/- 0.4 nl/min (P less than 0.001). When salt transport was inhibited by 10(-4) M furosemide in the perfusate, water absorption was 7.8 +/- 0.7 nl/min without suction and 6.1 +/- 0.8 nl/min with suction (P less than 0.01). Computer simulation of Henle's loop shows that these observations cannot be explained by changes in transit time, hydrostatic pressure, or unstirred layers. The observations are simulated when radial fluxes depend on wall thickness and surface area in the descending thin limb.

Animals↗

PubMed1977

Evidence for a concentration gradient favoring outward movement of sodium from the thin loop of Henle.

Recent models of the urinary concentrating mechanism have postulated that urea in the medullary interstitium creates a transtubular concentration gradient for sodium between fluid at the end of the descending limb of Henle's loop and the medullary interstitium, favoring the passive outward movement of sodium from Henle's thin ascending limb. These experiments were designed to determine whether such a gradient normally exists. Young nondiuretic Munich-Wistar rats were prepared for micropuncture of the exposed left renal papilla. Samples of loop of Henle fluid and vasa recta plasma (assumed to reflect the composition of interstitial fluid) were obtained from adjacent sites. Loop fluid values in 21 comparisons from 18 rats (mean +/- SE) were: sodium 344 +/- 12 meq/liter; potassium, 26 +/- 2 meq/liter; osmolality, 938 +/- 37 mosmol/kg H23. Vasa recta plasma values (in corresponding units of measurement) were: sodium, 284 +/- 11; potassium, 34 +/- 2; osmolality, 935 +/- 34. Mean values of paired differences (loop fluid minus vasa recta plasma) were: delta sodium, 60 +/- 11.1 (P less than 0.001); delta potassium, -8.0 +/- 2.1 (P less than 0.001); delta osmolality, 4 +/- 16 (NS). Corrected for plasma water, the loop fluid minus vasa recta differences (in milliequivalents per kilogram H2O) were: delta sodium, 40 +/- 11.4 (P less than 0.005); delta potassium, -9.7 +/- 1.9 (P less than 0.001). We interpret these findings to indicate that in the papilla of nondiuretic rats, a significant difference in sodium concentration exists across the thin loop of Henle favoring outward movement of sodium, which confirms a key requirement of the passive models. A concentration difference for potassium in the reverse direction was also observed.

Animals↗

PubMed1986

Distribution of Henle's loops may enhance urine concentrating capability.

A simple mathematical model that was developed by Charles S. Peskin (unpublished manuscript) for a single nephron is introduced and then extended to reflect the decreasing loop of Henle population as a function of increasing medullary depth. In the model, if all the loops turn at the same depth, the concentrating capability is limited by a factor of e over plasma osmolality. However, a decreasing loop population causes a multiplier effect that greatly enhances the concentrating capability. Using the loop distribution of the rat, the model produces a sigmoidal osmolality profile similar to the profiles found in tissue-slice studies of rat kidneys. These model calculations suggest that the decreasing nephron population found in vivo may be an important factor in the concentrating mechanism of the mammalian kidney.

Animals↗

PubMed1986

Development of differentiated characteristics in cultured kidney (thick ascending loop of Henle) cells.

This study describes the characterization of epithelial cells in culture following their isolation from the thick ascending limb of Henle's loop of rabbit kidney, by enzymatic digestion and subsequent purification using density gradient centrifugation. In culture, these cells expressed a variety of morphological, enzymatic and functional parameters expected of such cells in vivo. These cells were polarised, formed tight junctions and exhibited considerable lateral interdigitation between adjacent cells. They also developed characteristically high levels of activity of Na,K-ATPase, comparable to those seen in freshly isolated cells, and also expressed the functionally important Na,K,Cl-co transport system. The development of these systems in culture, however, was not coincident and their activities were reduced upon extended culture. The ability of these cells to develop and express differentiated characteristics in culture indicates that cells derived from defined kidney cell populations should provide valuable models for the study of the factors involved in the development and regulation of kidney cell type-specific characteristics.

Alkaline Phosphatase↗

PubMed1978

[Ion excretion by the rat kidney in depressed reabsorption in proximal tubule and ascending protion of the loop of Henle].

Simultaneous suppression of reabsorption in the proximal tubule with the aid of polyethylenglucole 400 (PEG) and in ascending part of Henle's loop with furosemide increased diuresis by 121 times and natri-uresis by 242 times on the average. The increase was based on changes in the tubule reabsorption and secretion. The changes of sodium and calcium excretion as well as excretion of potassium and magnesium were parallel. Excretion of sodium and calcium was lesser than the diuresis while that of magnesium and potassium exceeded it. Furosemide reduced the reabsorption of osmotically free water.

Absorption↗

PubMed1982

Thick ascending limb of Henle's loop.

Thick ascending limbs of Henle's loop have at least three major roles: (1) They reabsorb sodium chloride which dilutes the urine. (2) The reabsorption of sodium chloride also produces concentration gradients that drive the countercurrent multiplier system in the medulla and medullary rays and thus concentrates the urine. (3) They reabsorb large amounts of potassium, calcium, and magnesium in an energy-efficient manner. The mechanisms involved in these functions are reviewed in this paper, emphasizing the results of direct studies on isolated tubule segments.

Aldosterone↗

PubMed1979

Voltage dependence of calcium transport in the thick ascending limb of Henle's loop.

Thick ascending limbs of Henle's loop were dissected from rabbit kidneys and perfused in vitro. Unidirectional transepithelial calcium fluxes from lumen-to-bath and bath-to-lumen were measured with 45Ca using different solutions that caused the transepithelial voltage to vary over a wide range. With lumen-positive voltages there was net calcium absorption from lumen to bath which varied directly with the voltage. With voltage near zero there was no measurable net flux. When the voltage was made negative, the direction of net calcium transport reversed (i.e., secretion from bath to lumen). The presence or absence of bicarbonate in the lumen did not affect the calcium fluxes. Calcium permeability, calculated from the dependence of net flux on voltage, was 7.7 x 10(-6) cm/s, which is approximately 25% of the sodium permeability previously determined in this segment. Analysis of the calcium flux ratios revealed interdependence of the bidirectional fluxes consistent with single-file diffusion but no evidence for active calcium transport. We conclude that there is an important component of passive net calcium transport driven by the voltage in this segment.

Animals↗