Nephron function of the isolated perfused rat kidney

1976 ◽  
Vol 231 (6) ◽  
pp. 1699-1707 ◽  
Author(s):  
G De Mello ◽  
T Maack
Keyword(s):  
Transit Time ◽  
Filtration Rate ◽  
Rat Kidney ◽  
Mean Values ◽  
Isolated Perfused Rat Kidney ◽  
Henle's Loop ◽  
Perfused Rat Kidney ◽  
Fluid Load ◽  
Single Nephron ◽  
Distal Tubules

Nephron functions of an improved isolated perfused rat kidney preparation were studied by micropuncture techniques. Single-nephron glomerular filtration rate (SNGFR), intratubular pydrostatic pressures (IP), transit time (TT), and the reabsorption (R) of H2O, Na, Cl, and K were measured in superficial proximal (PT) and distal tubules (DT) of the preparation. Mean SNGFR was 27.2 nl/min and 25.2 nl/min when measured in PT and DT, respectively. The PT transport functions were well maintained throughout the perfusion (mean values were: IP, 14.3 mmHg; TT, 17.7 s; fractional (F) RH2O, 64%; absolute RH2O, 15.4 nl/min; FRNA, 66.5%; FRK, 71%, and tubular fluid-to-perfusate tf/p) ratio of Cl, 1.37). The short loops of Henle reabsorbed less than 10% of the load of H2O and Na delivered to them and the TF/P ratio of electrolytes in the earliest DT segments were high (TF/P)Na = 0.88, (TF/P)Cl = 1.27, and (TF/P)K = 1.11). This deficiency in function of Henle's loop explains, at least in part, the degree of natriuresis of the preparation (overall FRNa = 97.5%). Transit time to end DT was prolonged (82.3 S) and IP in DT elevated (14.9 mmHg). The DT was able to compensate, in part, for the overload from Henle's loop by reabsorbing 36% of the fluid load and 54% of the Na load delivery to it. We concluded that the improved isolated perfused rat kidney is a suitable preparation with which to study several aspects of renal function, particularly proximal tubules transport functions.

Endothelin-3 Modulates Glomerular Filtration Rate in the Isolated Perfused Rat Kidney

1992 ◽  
Vol 15 (6) ◽  
pp. 325-333 ◽  
Author(s):  
H. Schramek ◽  
C.C. Willinger ◽  
G. Gstraunthaler ◽  
W. Pfaller
Keyword(s):  
Glomerular Filtration Rate ◽  
Glomerular Filtration ◽  
Filtration Rate ◽  
Rat Kidney ◽  
Isolated Perfused Rat Kidney ◽  
Perfused Rat Kidney ◽  
Endothelin 3

scholarly journals Renal Disposition of Colistin in the Isolated Perfused Rat Kidney

2009 ◽  
Vol 53 (7) ◽  
pp. 2857-2864 ◽  
Author(s):  
Zheng Ma ◽  
Jiping Wang ◽  
Roger L. Nation ◽  
Jian Li ◽  
John D. Turnidge ◽  
...  
Keyword(s):  
Rat Kidney ◽  
Tubular Reabsorption ◽  
Mean Values ◽  
Isolated Perfused Rat Kidney ◽  
Renal Disposition ◽  
Perfused Rat Kidney ◽  
Renal Clearances ◽  
The Mean ◽  
Potential Inhibitors

ABSTRACT Nephrotoxicity is an important limitation to the clinical use of colistin against Pseudomonas aeruginosa and other gram-negative pathogens. Previous work reported net tubular reabsorption of colistin by the kidney in vivo, but there is no knowledge of its disposition within the kidney. This study investigated the renal disposition and potential transport mechanisms of colistin in the isolated perfused rat kidney (IPK) model by perfusing with colistin sulfate alone (2 μg/ml) or in the presence of potential inhibitors (tetraethylammonium [TEA], glycine-glycine [Gly-Gly], or hydrochloric acid [HCl]) at three different concentrations. When perfused alone, the renal clearances (CLR) for colistin A and B (the major components of colistin) in control kidneys were constant and low (mean values < 0.05 ml/min throughout the perfusion). The mean clearance ratios [CR, defined as CLR/(f u × GFR), where f u is the fraction of drug unbound in perfusate and GFR is the glomerular filtration rate] were significantly less than 1. It was concluded that there is net tubular reabsorption of colistin, and this exceeded the reabsorption of water. Less than 10% eliminated from perfusate was recovered in urine, suggesting considerable renal accumulation of colistin. The CR values for colistin were significantly increased when perfused with TEA (500 μM), Gly-Gly (833 μM), and HCl (2,500, 5,000, and 10,000 μM). It is proposed that renal reabsorption of colistin may involve organic cation transporters (inhibited by TEA) and peptide transporters (inhibited by Gly-Gly) and that the process is sensitive to the pH of urine.

31P nuclear magnetic resonance study of steady-state adenosine 5′-triphosphate levels during graded hypoxia in the isolated perfused rat kidney

1988 ◽  
Vol 74 (4) ◽  
pp. 437-448 ◽  
Author(s):  
P. J. Ratcliffe ◽  
Z. H. Endre ◽  
S. J. Scheinman ◽  
J. D. Tange ◽  
J. G. G. Ledingham ◽  
...  
Keyword(s):  
Steady State ◽  
Proximal Tubule ◽  
Oxygen Delivery ◽  
Rat Kidney ◽  
Thick Ascending Limb ◽  
Cellular Injury ◽  
Isolated Perfused Rat Kidney ◽  
Medullary Thick Ascending Limb ◽  
Henle's Loop ◽  
Perfused Rat Kidney

1. A model of controlled hypoxia in the isolated perfused rat kidney has been used to compare the extent of reduction in the steady-state level of adenosine 5′-triphosphate (ATP) from that initially observed with alterations in renal function and with the development of tubular cell injury. 2. ATP depletion was observed in response to decreased total oxygen delivery even when delivery greatly exceeded consumption and the venous oxygen tension remained in excess of 150 mmHg. 3. Increases in the fractional excretion of sodium occurred progressively below an apparent threshold value of whole kidney ATP of approximately 80% of the baseline. 4. With modestly decreased oxygen delivery, cellular injury was confined to deep proximal tubule and medullary thick ascending limb of Henle's loop. Severely decreased oxygen delivery rates were associated with cellular damage spreading throughout the cortex. 5. Even the smallest reductions in whole kidney ATP were associated with morphological damage to tubular cells. The extent of reduction in whole kidney ATP was closely correlated and approximately equivalent to the calculated volume of injured cells. 6. Our results indicate that reduction in whole kidney ATP during decreased oxygen delivery is a valid marker of the extent of injurious cellular hypoxia and are consistent with the view that cellular ATP concentrations in hypoxia are markedly inhomogeneous. They support the hypothesis that specific regions of the perfused kidney become critically hypoxic and develop cellular injury while overall oxygen delivery remains high. Areas at risk include deep proximal tubule as well as the medullary thick ascending limb of Henle's loop.

Physiological evaluation of the isolated perfused rat kidney

1980 ◽  
Vol 238 (2) ◽  
pp. F71-F78 ◽  
Author(s):  
T. Maack
Keyword(s):  
Rat Kidney ◽  
Critical Evaluation ◽  
Proximal Convoluted Tubule ◽  
Urinary Concentration ◽  
Isolated Perfused Rat Kidney ◽  
Low Viscosity ◽  
Metabolic Functions ◽  
Perfusate Flow ◽  
Perfused Rat Kidney ◽  
Single Nephron

A critical evaluation of the functional properties of the isolated perfused rat kidney is necessary to assess the usefulness of the preparation for renal function studies. Clearance and micropuncture experiments in isolated perfused rat kidneys perfused with a plasmalike medium containing 7.5 g/100 ml albumin, glucose, and amino acids show that proximal convoluted tubule functions are well preserved. Proximal convoluted tubule reabsorption of organic substances, electrolytes, and fluid is near normal, the latter being directly related to the peritubular oncotic pressure. Superficial single nephron glomular filtration rate and glomerular permselectivity are also preserved. However, abnormalities in renal hemodynamics, urinary concentration-dilution, and excretion of fluid and electrolytes persist even in the best preparations. High renal perfusate flow, due mainly to the low viscosity of the perfusate, and altered distal nephron functions explain at least in part these abnormalities. Therefore, the isolated perfused rat kidney is a useful preparation to particularly study glomerular and proximal convoluted tubule functions. Recent development of a nonfiltering isolated perfused rat kidney model, with preserved renal perfusate flow and cellular integrity, also permits the study of transport and metabolic functions of proximal tubular cells independently of luminal events.

The Vulnerability of the Thin Descending Limbs of Henle's Loop in the Isolated Perfused Rat Kidney

1989 ◽  
Vol 14 (1) ◽  
pp. 25-30 ◽  
Author(s):  
Juri Kopolovic ◽  
Mayer Brezis ◽  
Kate Spokes ◽  
Patricio Silva ◽  
Frank Epstein ◽  
...  
Keyword(s):  
Rat Kidney ◽  
Isolated Perfused Rat Kidney ◽  
Henle's Loop ◽  
Perfused Rat Kidney

Renal secretion of [35-S]furosemide and depression by albumin binding

1975 ◽  
Vol 229 (1) ◽  
pp. 93-98 ◽  
Author(s):  
RH Bowman
Keyword(s):  
Bovine Serum Albumin ◽  
Serum Albumin ◽  
Bovine Serum ◽  
Filtration Rate ◽  
Rat Kidney ◽  
Secretory Process ◽  
Albumin Binding ◽  
Renal Secretion ◽  
Isolated Perfused Rat Kidney ◽  
Perfused Rat Kidney

It was determined by use of [35-S]furosemide and an ultrafiltration procedure that furosemide is bound extensively to bovine serum albumin. When 500 muM furosemide and albumin at a concentration of 2.5 g/100 ml were used, approximately 90% of the drug was bound. With this same amount of furosemide, but with 3 times as much albumin, binding was about 98%. Using a 25-fold lower concentration of furosemide, 20 muM, binding was nearly 98% with 2.5 g albumin/100 ml, and was over 98% with 7.5 g albumin/100 ml. These same concentrations of furosemide and albumin were used to investigate the excretory and secretory rates of [35-S]furosemide in the isolated perfused rat kidney. Tubular clearance (i.e., secretion) of [35-S]furosemide was inversely related to the concentration of albumin in the perfusate. In kidneys perfused without albumin, tubular clearance of the drug was 6-20 times that found when 2.5 or 7.5 g albumin/100 ml, respectively, was used. Probenecid, with or without albumin, reduced the clearance of furosemide to that of its filtration rate. It is concluded that at physiological albumin concentrations, a very small fraction of circulating furosemide will be available for filtration, and tubular-fluid and urinary furosemide will arise predominantly from secretion. Because of extensive binding of furosemide to albumin, the renal secretory process itself is depressed, and the rate of secretion will be dependent, in part, on the concentration of unbound drug.

Effect of Polycations on the Function of the Isolated Perfused Rat Kidney

1990 ◽  
Vol 79 (6) ◽  
pp. 591-598 ◽  
Author(s):  
J. D. Firth
Keyword(s):  
Molecular Weight ◽  
Vascular Resistance ◽  
Filtration Rate ◽  
Rat Kidney ◽  
Minimal Change Nephrotic Syndrome ◽  
High Concentration ◽  
Heavy Proteinuria ◽  
Isolated Perfused Rat Kidney ◽  
Filtration Barrier ◽  
Perfused Rat Kidney

1. In minimal change nephrotic syndrome the occurrence of heavy proteinuria can be explained on the basis of a reduction in charge selectivity of the glomerular filtration barrier, and it has been proposed that this might be caused by the neutralization of anionic groups by a circulating polycationic factor. 2. The effects of two polycations, protamine and poly-l-lysine, on the function of the isolated perfused rat kidney have been examined. 3. Poly-l-lysine polymers of relatively high molecular weight (8800 and 17800) induced heavy proteinuria, while simultaneously causing a marked increase in renal vascular resistance and a fall in filtration rate. Protamine (approximate molecular weight 7000) at relatively high concentration induced modest proteinuria in the absence of effects on vascular resistance or filtration rate. 4. A poly-l-lysine polymer of lower molecular weight (3800) did not induce proteinuria. Protamine at a concentration of 40 μg/ml and below did not affect protein excretion either. Both provoked substantial natriuresis. This appeared to be largely due to an effect on the tubular handling of sodium since the filtration rate remained steady while fractional sodium excretion rose markedly. 5. The natriuretic effect of protamine was blocked by heparin, but not by indomethacin or verapamil, suggesting that the mechanism of natriuresis did not depend upon either prostaglandin production or entry of calcium through verapamil-sensitive channels.

Natriuretic and kaliuretic activities of guanylin and uroguanylin in the isolated perfused rat kidney

1998 ◽  
Vol 275 (2) ◽  
pp. F191-F197 ◽  
Author(s):  
Manasses C. Fonteles ◽  
Richard N. Greenberg ◽  
Helena S. A. Monteiro ◽  
Mark G. Currie ◽  
Leonard R. Forte
Keyword(s):  
Glomerular Filtration Rate ◽  
Glomerular Filtration ◽  
Filtration Rate ◽  
Biological Effects ◽  
Rat Kidney ◽  
Second Messenger ◽  
Maximal Increase ◽  
Isolated Perfused Rat Kidney ◽  
Water Homeostasis ◽  
Perfused Rat Kidney

Guanylin and uroguanylin are novel peptides that activate membrane guanylate cyclases found in the kidney and intestine. We compared the effects of these peptides in the isolated perfused rat kidney. Both peptides are natriuretic and kaliuretic in this preparation. Uroguanylin (0.19–1.9 μM) increased glomerular filtration rate from 0.77 ± 0.07 to 1.34 ± 0.3 ml ⋅ g−1⋅ min−1at the highest concentration. A maximal increase in Na+excretion was achieved at 0.66 μM uroguanylin, with a reduction in fractional Na+reabsorption from 78.7 ± 1.7 to 58.8 ± 4.4%. The highest dose of uroguanylin increased kaliuresis by 50%. Osmolar clearance doubled at the highest concentration of uroguanylin tested ( P< 0.05). Guanylin also elicited a natriuresis and kaliuresis but appeared to be less potent than uroguanylin. The highest concentration of guanylin (1.3 μM) decreased fractional Na+reabsorption from 73.9 ± 2.4 to 64.5 ± 4.0%, but lower doses were ineffective. Guanylin stimulated urine K+excretion at the lowest concentration tested (0.33 μM) without any effect on Na+excretion. These peptides may influence salt and water homeostasis by biological effects in the kidney that are mediated by the intracellular second messenger, cGMP.

Validation of a toxicity testing model by evaluating oxygen supply and energy state in the isolated perfused rat kidney

1991 ◽  
Vol 25 (3) ◽  
pp. 195-204 ◽  
Author(s):  
Takano Takehito ◽  
Nakata Kazuyo ◽  
Kawakami Tsuyoshi ◽  
Miyazaki Yoshifumi ◽  
Murakami Masataka ◽  
...  
Keyword(s):  
Oxygen Supply ◽  
Energy State ◽  
Rat Kidney ◽  
Toxicity Testing ◽  
Testing Model ◽  
Isolated Perfused Rat Kidney ◽  
Perfused Rat Kidney
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