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At least 343 records · Page 19Linked to original sources
PubMed1999

Cell shrinkage triggers the activation of mitogen-activated protein kinases by hypertonicity in the rat kidney medullary thick ascending limb of the Henle's loop. Requirement of p38 kinase for the regulatory volume increase response.

The kidney medulla is exposed to very high interstitial osmolarity leading to the activation of mitogen-activated protein kinases (MAPK). However, the respective roles of increased intracellular osmolality and of cell shrinkage in MAPK activation are not known. Similarly, the participation of MAPK in the regulatory volume increase (RVI) following cell shrinkage remains to be investigated. In the rat medullary thick ascending limb of Henle (MTAL), extracellular hypertonicity produced by addition of NaCl or sucrose increased the phosphorylation level of extracellular signal-regulated kinase (ERK) and p38 kinase and to a lesser extent c-Jun NH(2)-terminal kinase with sucrose only. Both hypertonic solutions decreased the MTAL cellular volume in a dose- and time-dependent manner. In contrast, hypertonic urea had no effect. The extent of MAPK activation was correlated with the extent of MTAL cellular volume decrease. Increasing intracellular osmolality without modifying cellular volume did not activate MAPK, whereas cell shrinkage without variation in osmolality activated both ERK and p38. In the presence of 600 mosmol/liter NaCl, the maximal cell shrinkage was observed after 10 min at 37 degrees C and the MTAL cellular volume was reduced to 70% of its initial value. Then, RVI occurred and the cellular volume progressively recovered to reach about 90% of its initial value after 30 min. SB203580, a specific inhibitor of p38, almost completely inhibited the cellular volume recovery, whereas inhibition of ERK did not alter RVI. In conclusion, in rat MTAL: 1) cell shrinkage, but not intracellular hyperosmolality, triggers the activation of both ERK and p38 kinase in response to extracellular hypertonicity; and 2) RVI is dependent on p38 kinase activation.

Animals↗
PubMed1986

Effects of glucagon and PTH on the loop of Henle of rat juxtamedullary nephrons.

We investigated by micropuncture the effects of glucagon and parathyroid hormone (PTH) on thin limbs of juxtamedullary nephrons of rats with reduced plasma concentration of endogenous glucagon, PTH, antidiuretic hormone (ADH) and calcitonin, all four hormones enhancing the adenylate-cyclase activity in the thick ascending limbs and the distal nephron. Such a hormonal depletion suppresses the corticomedullary concentration gradient, making favourable conditions for studying the influence of these hormones on the renal concentrating mechanism. Administration of glucagon (4.4 ng/min-1) or PTH (5 mU/min-1) to these hormone-deprived rats elicited the expected decrease in urinary Mg and Ca fractional excretion without modifying either fractional or absolute excretion of water. At the tip of the loop, glucagon enhanced the loop fluid osmolality by 20%, but left the delivery of water unchanged. The Na and Cl concentrations increased significantly with the osmolality, resulting in a positive correlation between the fractional delivery of either ion and the loop fluid osmolality. PTH increased the fraction of filtered phosphate delivered to the thin limbs, as expected, but, in contrast to glucagon, did not alter either the Na, Cl, or total solute fractional deliveries. The Mg, Ca and K deliveries were unaffected by glucagon and PTH. In conclusion, glucagon, which activates the cyclase system of both the medullary and cortical portion of the thick ascending limb, enhances the delivery of salt to the tip of the loop by net sodium chloride addition to the descending limb. PTH which activates the adenyl-cyclase system only in the cortical thick ascending limb cannot enhance such NaCl delivery. NaCl, when added, might therefore originate from the medullary thick ascending limb.

Adenylyl Cyclases↗
PubMed1978

Physical properties of isolated perfused basement membranes from rabbit loop of Henle.

Isolated, perfused segments of late proximal straight tubule, descending thin limb of Henle, and ascending thick limb of Henle from the rabbit were studied before and after removal of the epithelium with sodium deoxycholate. The relationship between transmural hydrostatic pressure and outer tubule diameter was similar in paired intact tubules and basement membranes, indicating that basement membrane is the principal determinent of tubule distensibility. As calculated from teh measured perfusate flow at several different transmembrane hydrostatic pressures, the hydraulic conductivity of the basement membranes was 6-8 X 10(-3) cm3/cm2.min.cmH2O. With use of these LP values and the calculated oncotic pressure required experimentally to reduce transmembrane hydrostatic pressure transiently to zero, the apparent reflection coefficient of the basement membranes for serum albumin was estimated to be 0.05-0.16. It is concluded that basement membranes of the loop and of other previously studied segments of rabbit nephron provide very strong and elastic mechanical support to the epithelium while having minimal resistance to flow of water and of solutes as large as serum albumin.

Animals↗
PubMed1994

[The thick ascending limb of the loop of Henle: a key segment in the renal regulation of acid-base status?].

The thick ascending limb (TAL) of rat kidney has been shown to reabsorb bicarbonate and NH4+. Therefore, in vivo and in vitro studies have demonstrated that bicarbonate absorption by the medullary TAL (mTAL) is influenced by peptide hormones (AVP, PTH), prostaglandin, osmolality and chronic metabolic acidosis. AVP, whose major effect is water balance regulation, also modulates acid-base handling in the mTAL, and then contribute to the regulation of renal acid excretion. These data suggest that the TAL could play an important role in the physiology and pathology of acid-base status.

Absorption↗
PubMed1989

Single nephron comparison of the effect of loop of Henle flow on filtration rate and pressure in control and angiotensin II-infused rats.

Experiments were performed in control and angiotensin II-infused rats to test whether the tubuloglomerular feedback responses of early proximal flow rate (VEP) and stop flow pressure (PSF) are elicited by the same flow rate changes. Paired measurements in the same nephron revealed that VEP responses were shifted to the left compared to those of PSF. The flow rate at which the response was half maximum, V1/2, was 14.7 +/- 1.25 nl/min for VEP and 18.9 +/- 0.97 nl/min for PSF (p less than 0.05). This difference in flow dependency was abolished by angiotensin II infusion (V1/2 was 14.6 +/- 0.87 nl/min for VEP and 15.4 +/- 1.09 nl/min for PSF). Furthermore, angiotensin infusion markedly augmented the feedback response magnitude.

Angiotensin II↗
PubMed1986

Torasemide inhibits NaCl reabsorption in the thick ascending limb of the loop of Henle.

Torasemide (1-isopropyl-(4-(3-methylphenylamino)pyrid-3-yl)urea) is a new diuretic. The present study examines the effects of this substance in the isolated perfused thick ascending limb (TAL) of mouse and rabbit kidney. In cortical TAL segments of the rabbit, torasemide added to the lumen perfusate led to a fall in equivalent short circuit current ( = transepithelial voltage divided by transepithelial resistance, which corresponds to the rate of chloride reabsorption) with a half maximal inhibition concentration of 3 X 10(-7) mol/l. This effect was accompanied by a hyperpolarization of the luminal and basolateral membrane from -78 to -81 mV and from -72 to -81 mV, respectively. A similar hyperpolarization of both membrane voltages was also observed in medullary TAL segments of the mouse. Torasemide, added to the basolateral perfusate of cortical TAL segments of the rabbit, also inhibited the equivalent short circuit current. However, 3 X 10(-5) mol/l were necessary for a half maximal inhibition. The fall in the equivalent short circuit current was accompanied by a significant increase in transepithelial resistance from 34 to 38 omega cm2, by an increase in the fractional resistance of the basolateral membrane, and by a hyperpolarization mainly of the basolateral membrane. Again, similar results were obtained in the medullary TAL segment of the mouse. The strong inhibitory effect of torasemide from the lumen side can be explained by an interference with the Na+ 2Cl-K+ carrier in the luminal membrane. In fact, torasemide apparently is structurally related to furosemide.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Effect of synthetic ANP on renal and loop of Henle functions in the young rat.

The present studies were undertaken to determine, by recollection micropuncture, the effect of a synthetic atrial natriuretic peptide (ANP) on the absolute and fractional deliveries of water and sodium to the juxtamedullary end-descending limb. Two groups of young female Munich-Wistar rats were studied: control (n = 8) received the vehicle only; and ANP (n = 12) received a prime followed by the constant infusion of a synthetic rat atrial peptide (28 amino acids). With the infusion of ANP, clearance of p-[14C]aminohippurate [( 14C]PAH) and glomerular filtration rate (GFR) fell significantly. Despite this fall in GFR and renal plasma flow, ANP produced a 2-fold increase in urine volume and a 10-fold increase in sodium excretion. Absolute and fractional sodium deliveries to the end-descending limb increased by approximately 30% in the ANP group, whereas mean juxtamedullary single-nephron glomerular filtration rate (SNGFR) remained stable. In three additional rats prepared for micropuncture of the superficial end-accessible proximal tubule, ANP reduced cortical SNGFR by approximately 15%. By contrast, GFR did not decline in response to ANP in larger rats, when treated identically. We conclude that in young rats ANP can produce a natriuresis in the absence of a rise in GFR; the fall in GFR observed following ANP is due presumably to the immaturity of the animals used in these studies; and ANP produces a rise in absolute and fractional water and sodium deliveries to the end-descending limb that cannot be attributed to a change in SNGFR.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Analogues of torasemide--structure function relationships--experiments in the thick ascending limb of the loop of Henle of rabbit nephron.

The aim of the present study was to examine compounds related to torasemide with respect to their ability to block the equivalent short circuit current, corresponding to the rate of chloride reabsorption, in isolated in vitro perfused cortical thick ascending limbs of Henle of the rabbit. The torasemide molecule was modified with respect to the anionic sulfonylurea group, and the secondary amine linked to the pyridine ring. Our results indicate that only few of the tested 48 torasemide-related compounds were able to inhibit from both epithelial sides like torasemide. Only few of the tested compounds were equally effective as torasemide from the lumen side. Some analogues were acting only from the luminal side and some only from the peritubular side. The correlations between structure and potency of inhibition from the luminal side allow the following conclusions: The secondary amine moiety linked to the pyridine ring (toluidine in case of torasemide) can be replaced by a cycloalkylamine or, with some loss of inhibitory potency, by alkylamines. The inhibitory potency is increased with the number of C-atoms in the cycloalkylamine substituted compounds (optimum C7 to C8) and is also depending on the length of the alkylamines (optimum C4). The secondary amine seems to be required since nitrogen cannot be replaced by -S- or -SO2-. The sulfonylurea group cannot be substituted by other anionic groups such as -SO-3 or -COO-. If the pyridine ring is replaced by a NO2-substituted phenyl ring, the inhibitory potency from the luminal side is lost. However, these compounds act still (with some loss of potency) from the peritubular side.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2004

Three-dimensional lateral and vertical relationships of inner medullary loops of Henle and collecting ducts.

Functional reconstruction of inner medullary thin limbs of Henle and collecting ducts (CDs) has enabled us to characterize distinctive three-dimensional vertical and lateral relationships between these segments. We previously reported that inner medullary descending thin limbs (DTLs) that form a bend at a distance greater than approximately 1 mm below the inner medullary base express detectable aquaporin (AQP) 1 only along the initial 40% of the segment before the bend, whereas ClC-K1 is expressed continuously along all ascending thin limbs (ATLs), beginning with the prebend segment. We have now reconstructed individual CDs that are grouped together in single clusters at the base of the inner medulla; CDs belonging to each separate cluster coalesce into a single CD in the deep papilla. DTLs are positioned predominantly at the periphery of each individual CD cluster at all levels of the inner medulla and are absent from within the cluster. In contrast, ATLs are distributed near uniformly among the CDs and DTLs at all levels of the inner medulla. A second population of inner medullary DTLs averages approximately 700 microm in length from base to bend and, as previously reported, expresses no detectable AQP1 and expresses ClC-K1 continuously beginning with the prebend segment. ATLs located within the interior of the CD clusters arise predominantly from these short AQP1-null inner medullary DTLs, suggesting there may be functional interdependence between IMCD1 segments and short-length inner medullary thin limbs exhibiting minimal water permeability along their descending segments. AQP1-expressing DTLs and CDs are apparently separated into two structurally distinct lateral compartments. A similar lateral compartmentation between the ATLs and CDs is not apparent. This architectural arrangement indicates that fluid and solutes may be preferentially transported transversely between multiple inner medullary compartments.

Animals↗
PubMed1975

Freeze-fracture differences between plasma membranes of descending and ascending branches of the rat Henle's thin loop.

Freeze-fracture of Henle's thin loop of the rat shows that the plasma membrane of epithelial cells in the descending branch has far more particles (approximately 4000 per sq. mum.) than the plasma membrane in the ascending branch (approximately 1000 per sq. mum). On the contrary, the tight junctions between epithelial cells in the two branches are equally developed. The large number of particles in the descending branch may be an important factor in the water permeability of this tubular segment.

Animals↗
PubMed1997

[The effect of a low-protein diet on the epithelium of nephron segments in sheep].

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.

Animal Nutritional Physiological Phenomena↗