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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of anion-transport inhibitors on volume reabsorption, and total CO(2) concentrations were examined by in vivo microperfusion of superficial proximal convoluted tubules of rats. The luminal perfusion solution was a high-chloride, low-bicarbonate solution like that in the in vivo late proximal tubule. The anion-transport inhibitors were only added to the luminal perfusion solutions. In tubules perfused with the control high-chloride solution, the rate of volume reabsorption (J(v)) was 2.3+/-0.2 nl/mm.min (n = 18), and the collected total CO(2) concentration was 4.0+/-0.3 mM. Furosemide (3 mM) caused a marked reduction in volume reabsorption to 0.8+/-0.3 nl/mm.min (n = 20) and only a slight increase in the total CO(2) concentration of collected samples of perfusate (7.8+/-0.5 mM). 0.8 mM acetazolamide caused a more pronounced rise in the collected total CO(2) concentrations to 10.7+/-0.5 mM but only a slight fall in J(v) to 1.7+/-0.3 nl/mm.min (n = 19). Hence, we inferred that inhibition of carbonic anhydrase only partially accounted for the inhibition of J(v) by furosemide. 4-acetamido-4'-iso-thiocyanato-stilbene-2,2'-disulphonic acid (0.1 mM), a well-characterized inhibitor of erythrocyte anion exchange mechanisms, also reduced J(v) to 1.6+/-0.3 nl/mm.min (n = 15) without changing the total CO(2) concentrations of the collected perfusates (3.6+/-0.4 mM). The effect of 4-acetamido-4'-iso-thiocyanato-stilbene-2,2'-disulphonic acid on volume reabsorption could not be explained by carbonic anhydrase inhibition because there was no increase in the total CO(2) concentration of the collected fluids. Furosemide did not significantly inhibit the rate of tracer glucose efflux out of the tubules, which suggests that the effect of furosemide on volume reabsorption was not a result of some nonspecific depression of active sodium transport. These results are discussed with respect to the possible effects of anion-transport inhibitors on the paracellular shunt pathway, active sodium reabsorption, and neutral sodium chloride transport.
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PMID:Effects of anion-transport inhibitors on NaCl reabsorption in the rat superficial proximal convoluted tubule. 45 69

The separate administration of mercuric chloride (HgCl2) and sodium selenate (Na2SeO4) to male rats in drinking water or a combined administration of both (50 ppm Hg, 15 ppm Se) caused different signs of toxicity over a 22 week period. The HgCl2 group showed histopathological and ultrastructural lesions as evidenced by periportal fatty degeneration and cell necrosis in the liver and tubular necrosis with proteinaceous casts in the kidney. The Na2SeO4 group showed the most severe depression of growth and food and water consumption, but no pathological changes were seen in the liver or kidney. Simultaneous administration of both toxicants produced a protective effect on weight loss and histopathology. These effects were associated with the formation of electron dense nuclear inclusions in kidney proximal tubule cells and similar electron dense formations in the reticuloendothelial cell cytoplasm and in the extracellular space of Disse in the liver. These formations were shown to contain both Se and Hg by energy dispersive X-ray microanalysis. The basis of the protective interaction of these two elements appears to result from an alteration of the chemical form or association of the mercury and selenium.
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PMID:Effects of separate and combined chronic mercuric chloride and sodium selenate administration in rats: histological, ultrastructural, and x-ray microanalytical studies of liver and kidney. 54 21

The renal and proximal tubule response to contralateral kidney exclusion was studied in a variety of circumstances. Recollection micropuncture studies were performed to assess the response to contralateral kidney clamping in the normal or a remnant kidney of the dog. Acute clamping of the contralateral kidney for a normal and unilateral remnant kidney resulted in marked reduction in proximal TF/P inulin ratios in the experimental kidney reflecting a 15 percent reduction in fluid reabsorption. Mean fractional excretion of sodium, potassium and water increased significantly in remnant kidney dogs but no significant change was observed in normal dogs except for potassium excretion. The marked reduction in proximal reabsorption occurred as soon as 5-15 minutes after contralateral kidney clamping and was compensated by distal reabsorption. Acute obstruction of the contralateral ureter results in a similar markedly reduced proximal tubular reabsorption. The reduction in proximal reabsorption induced by contralateral clamping occurred in the presence of reduced perfusion pressure and volume expansion and to some extent with renal denervation. When prostaglandin E(2) or acetycholine were infused prior to contralateral kidney clamping, proximal reabsorption remained at control levels and the contralateral clamping response was blocked. Similar blockade occurred after treatment with indomethacin. Acute reduction in nephron mass causes a marked depression of proximal tubular sodium and fluid absorption not obviously accounted for by hemodynamicphysical factors and humoral factors may be involved. The level of distal reabsorption to increased proximal delivery following contralateral clamping, determines the net urinary excretion.
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PMID:Acute functional adaptation to nephron loss: micropuncture studies. 73 48

The intravenous injection of horseradish peroxidase (HRP) into rats of the Sprague-Dawley strain caused vascular leakage as detectable by a 20-40% increase in the hematocrit and a 15-20% decrease in plasma protein concentration. These changes did not occur when the same amounts of HRP were injected into rats pretreated with antagonists to histamine and serotonin. After pretreatment with the antagonists, the reabsorption of HRP by the proximal tubule cells (the concentration of HRP in the total particulate fractions) showed a 77% decrease and the urinary excretion of sodium showed more than an 80% increase as compared to the values from rats treated with HRP alone. In addition, the blood clearance rate of HRP was decreased and the urinary excretion of HRP was increased after treatment with the antagonists to histamine and serotonin. Cytochemical observations of formaldehyde vapor-fixed tissue also showed the effects of vascular leakage. After the injection of HRP in physiologic or hypertonic saline, the basal infoldings of the proximal tubule cells were strongly peroxidase-positive. When the same amounts of HRP were injected after pretreatment with antagonists to histamine and serotonin, or with mannitol, the basal infoldings were not stained or were stained faintly. Rats of the Wistar/Furth strain did not show the effects of vascular leakage observed with rats of the Sprague-Dawley strains. The questions are discussed as to whether the marked depression of renal cortical HRP absorption by mannitol and hypertonic saline (J Histochem Cytochem 23:707, 1975) is related to the prevention of vascular leakage, and whether the reabsorption of both sodium and protein is increased during the leakage of serum proteins into the interstitial tissue.
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PMID:Altered renal cortical reabsorption of protein and urinary excretion of sodium in relation to vascular leakage induced by horseradish peroxidase. 83 63

1. The ability of maturing rats to excrete a sodium load was studied by micropuncture and clearance procedures. 2. During control conditions, no change of glomerular filtration rate or sodium excretion was observed for the time period of the entire procedure (P greater than 0-20). During the infusion of hypertonic (4%) sodium chloride, fractional sodium excretion was 0-08 +/- 0-01 in rats 21-30 days old and 0-14 +/- 0-01 (P less than 0-01) in adults. However, the depression of proximal tubular water re-absorption was equal in both groups (P greater than 0-20). 3. Proximal glomerulotubular balance for water re-absorption was similar in all groups (P less than 0-20). Since end proximal tubular water excretion and depression of fractional water excretion were the same in all animals, differences of urinary sodium excretion during development are probably due to differences of function of segments beyond the proximal tubule during development. 4. Fractional potassium excretion was reduced in young rats (0-17 +/- 0-04) during hypertonic sodium chloride infusion, compared to adults (0-24 +/- 0-01, P less than 0-05). 5. Passage time of fast green through cortical segments in seconds is prolonged in young rats during control conditions. Similar decreases of passage time were seen in all groups during hypertonic sodium chloride infusion. No segmental differences of passage time were seen during developmental. 6. No difference in the relationship between fractional sodium and water excretion was seen during development of the renal response to hypertonic sodium chloride infusion. Thus, altered sensitivity to sodium chloride osmotic diuresis does not exist during maturation in rats.
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PMID:Maturation of the renal response to hypertonic sodium chloride loading in rats: micropuncture and clearance studies. 94 39

Studies were undertaken to characterize the renal responses to acute unilateral renal denervation and the mechanisms involved in these responses. Denervation was produced in anesthetized nondiuretic rats by application of phenol to the left renal artery. Studies were also performed in sham-denervated nondiuretic rats. Whole kidney and individual nephron studies were performed before and after denervation or sham denervation. Denervation increased urine volume from the left kidney to about twice its control value (P less than 0.001) and increased urinary sodium excretion from 332 neq min minus -1 to 1,887 neq min minus -1 (P less than 0.001). Glomerular filtration rate (GFR) and renal plasma flow (RPF) remained unchanged in both kidneys after the procedure. The innervated right kidney showed no changes in urine volume or in sodium excretion. After denervation, late proximal ratio of tubular fluid inulin concentration to that of plasma [(F/P)In] decreased from 2.23 to 1.50 (P less than 0.001) while single nephron GFR remained unchanged. Absolute reabsorption decreased from 16.5 to 9.9 n. min minus -1 (P less than 0.001). (F/P)In ratios were also decreased in early distal (from 6.21 to 3.18, P less 0.001) and late distal convolutions (from 16.41 to 8.33, P less than 0.001) during the experimental period. (F/P)Na ratios remained unchanged in the early distal convolutions, but increased from 0.18 to 0.38 (P less than 0.01) in late distal convolutions after denervation. Absolute Na reabsorption after denervation increased in the loop of Henle, distal convolution, and collecting ducts. Any changes in intrarenal hydrostatic pressures after denervation were always small. There were no changes in GFR, RPF, urine volume, urinary sodium excretion, or late proximal (F/P)In after sham denervation. We conclude that the diuresis and natriuresis seen after acute renal denervation were caused by a marked depression of sodium and water reabsorption in the proximal tubule with partial compensation in more distal nephron segments. These responses appeared to be unrelated to systemic or intrarenal hemodynamic changes. The results demonstrate an effect of the renal nerves on proximal tubular function.
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PMID:Effects of acute unilateral renal denervation in the rat. 114 32

The mechanism of inhibition of HCO3 transport by parathyroid hormone (PTH) in the proximal tubule is not clearly defined. Previous studies in vitro have suggested that this effect is mediated via cAMP generation, which acts to inhibit Na/H exchange, resulting in cell acidification. To examine this question in vivo, intracellular pH (pHi) was measured in the superficial proximal tubule of the rat using the pH-sensitive fluoroprobes 4-methylumbelliferone (4MU) and 2',7'-bis(carboxyethyl)-(5, and 6)-carboxyfluorescein (BCECF). PTH was found to alkalinize the cell. This alkalinization suggested inhibition of basolateral base exit, which was confirmed by in situ microperfusion studies: lowering HCO3 in peritubular capillaries acidified the cell, an effect blunted by PTH. Removal of luminal Na promoted basolateral base entry, alkalinizing the cell. This response was also blunted by PTH. Readdition of luminal Na stimulated the luminal Na/H exchanger, causing an alkalinization overshoot that was partially inhibited by PTH. cAMP inhibited luminal H secretion but did not alkalinize the cell. Stimulation of phosphatidylinositol-bis-phosphate turnover by PTH was suggested by the effect to the hormone to increase cell Ca. Blocking the PTH-induced rise in cell Ca blunted the effect of the hormone to alkalinize the cell, as did inhibition of phosphatidylinositol breakdown. Furthermore, stimulation of protein kinase C by a phorbol ester and a diacylglycerol applied basolaterally alkalinized the cell and inhibited luminal H secretion. The findings indicate that both arms of the phosphatidylinositol-bis-phosphate cascade play a role in mediating the effect of PTH on the cell pH. The results are consistent with the view that PTH inhibits base exit in the proximal tubule by activation of the phosphatidylinositol cascade. The resulting alkalinization may contribute, with cAMP, to inhibit apical Na/H exchange and the PTH-induced depression of proximal HCO3 reabsorption.
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PMID:Parathyroid hormone decreases HCO3 reabsorption in the rat proximal tubule by stimulating phosphatidylinositol metabolism and inhibiting base exit. 131 50

The proximal tubule model of this laboratory [Am. J. Physiol. 250 (Renal Fluid Electrolyte Physiol. 19): F860-F873, 1986] has been updated to examine proposed pathways for Cl- transport. Two additional buffer pairs have been added, i.e., HCO2-/H2CO2 and NH3/NH4+. At the luminal cell membrane Cl-/HCO2- and Cl-/HCO3- exchange are considered as pathways for Cl- entry, whereas at the peritubular membrane, Cl- exit occurs by either Na(+)-2HCO3-/Cl- exchange or K(+)-Cl- cotransport. Calculations with this model indicate that absolute proximal reabsorption of both Na+ and Cl- are critically dependent on the rate of luminal Na+/H+ exchange. In contrast, increases in the coefficient for Cl-/HCO2- exchange have little impact on overall Cl- flux, but, by enhancing base secretion, limit the depression of end-proximal HCO3-. Model calculations confirm those of Preisig and Alpern (J. Clin. Invest. 83: 1859-1867, 1989) showing that their measured value of luminal membrane H2CO2 permeability is inadequate to sustain the transcellular Cl- flux as Cl-/HCO2- exchange. Conversely, with sufficiently high H2CO2 permeability, luminal Cl- uptake is enhanced along the tubule, as HCO2- secretion and luminal acidification increase luminal H2CO2 to values severalfold greater than in glomerular filtrate. At the basolateral membrane, the thermodynamic driving force across the Na(+)-2HCO3-/Cl- exchanger is small. Although its contribution to steady-state Cl- exit may be less than the K(+)-Cl- cotransporter, the Na(+)-2HCO3-/Cl- exchanger can be a mechanism by which cytosolic acidification enhances peritubular Cl- transport, when luminal acidification enhances luminal Cl- uptake. A simulation is presented in which impermeant replacement of luminal Na+ leads to enhanced convective Cl- flux across the tight junction and alkalinization of the lateral interspace. In this setting, cytosolic Cl- depletion via the Na(+)-2HCO3-/Cl- exchanger may mimic luminal membrane Na(+)-Cl- cotransport.
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PMID:Chloride transport in a mathematical model of the rat proximal tubule. 144 69

Experiments were performed on rats to examine the cause of the vascular congestion that accompanies renal ischemia, and the potential role of cell swelling in its generation. Renal function and gross morphology were examined after reflow, whereas tissue morphometry was performed both before and after reflow in kidneys. Small doses of mannitol applied into the renal artery just before ischemia greatly reduced the incidence of vascular congestion and the depression of renal function. During ischemia the outwardly directed swelling of the proximal tubule depleted the interstitial and vascular space of the cortex and outer medullary outer stripe and the inwardly directed swelling of the thick ascending limb occluded the lumen. Mannitol reduced cell swelling, lessened the depletion of the interstitial and vascular space and eliminated the occlusion of the thick ascending limb. It is proposed that the loss of interstitial and vascular fluid during ischemia is the cause of the vascular congestion, which, in turn, is responsible for the poor perfusion and impaired renal function seen after ischemia.
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PMID:Vascular congestion in ischemic renal failure: the role of cell swelling. 249 26

1. Normotensive Sprague-Dawley and spontaneously hypertensive rats anaesthetized with sodium pentobarbitone were used to determine the systemic and renal actions of amlodipine, a new calcium channel blocking drug. 2. Amlodipine, 200 micrograms kg-1 plus 50 micrograms kg-1 h-1, decreased blood pressure by 12 +/- 3 mmHg in normotensive rats, although the fall was not statistically significant in the hypertensive rats; did not change renal haemodynamics and caused significant increases in urine flow, absolute and fractional sodium excretions of 70%, 91% and 113%, respectively, in normotensive rats and 65%, 91% and 96%, respectively in hypertensive rats. Fractional lithium excretion was unchanged in the normotensive rats but increased by 28% in the hypertensive animals while absolute fluid reabsorption in the proximal tubule did not change in either group. Absolute water and sodium reabsorption in the segments beyond the proximal tubule were unchanged in the normotensive rats but increased in the hypertensive animals by 24% and 22%, respectively, while fractional sodium excretion in this portion of the nephron increased by 88% and 51% in the normotensive and hypertensive rats, respectively. 3. Amlodipine, 400 micrograms kg-1 plus 100 micrograms kg-1 h-1, decreased blood pressure by 12 +/- 4 mmHg in the normotensive and by 27 +/- 5 mmHg in the hypertensive rats. Renal blood flow was not changed in either group of rats and glomerular filtration rate increased by 25% in the spontaneously hypertensive animals. There were significant increases in urine flow, absolute and fractional sodium excretions of 105%, 145% and 142%, respectively, in the normotensive rats and 224%, 421% and 259%, respectively, in the hypertensive rats. Renal blood flow was not changed in either group of rats and glomerular filtration rate increased by 25% in the spontaneously hypertensive animals. There were significant increases in urine flow, absolute and fractional sodium excretions of 105%, 145% and 142%, respectively, in the normotensive rats and 224%, 421% and 259%, respectively, in the hypertensive rats. Fractional lithium excretion was elevated by 29% and 38%, in the normotensive and hypertensive rats, respectively, but absolute fluid reabsorption at the proximal tubule remained unchanged. At the same time there were significant increases in absolute water and sodium reabsorption beyond the proximal tubule of 26% and 18%, respectively, in the normotensive animals and of 63% and 60%, respectively, in the hypertensive animals. Fractional excretion of water and sodium in the nephron regions after the proximal tubule were increased by 55% and 88%, respectively, in the normotensive rats and by 84% and 121%, respectively, in the hypertensive rats. 4. These doses of amlodipine caused modest reductions in blood pressure, minimal changes in renal haemodynamics and a natriuresis and diuresis. Proximal sodium and water reabsorption was not affected by the drug and it is suggested that the changes in tubular fluid handling were compatible with depression of reabsorption further along the tubule.
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PMID:A study of the renal actions of amlodipine in the normotensive and spontaneously hypertensive rat. 296 66


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