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.

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

Fate of [125I]insulin removed from the peritubular circulation of isolated perfused rat kidney

1982 ◽  
Vol 243 (2) ◽  
pp. F126-F132 ◽  
Author(s):  
J. Petersen ◽  
J. Kitaji ◽  
W. C. Duckworth ◽  
R. Rabkin
Keyword(s):  
Molecular Weight ◽  
Rat Kidney ◽  
Low Molecular Weight ◽  
Considerable Evidence ◽  
Isolated Perfused Rat Kidney ◽  
Mammalian Kidney ◽  
Perfused Rat Kidney ◽  
Specific Receptors ◽  
A Minor ◽  
Isolated Kidneys

Although there is considerable evidence that insulin is removed from the peritubular circulation of the mammalian kidney, it is unclear whether binding to insulin-specific receptors is involved in this process, whether after peritubular removal the hormone is degraded to small fragments with release into the circulation, or whether it merely undergoes a minor modification with loss of immunoreactivity. We examined the metabolism of [125I]insulin removed from the peritubular circulation of the nonfiltering isolated perfused rat kidney and compared it to that of [125I]insulin metabolized by filtering isolated kidneys and kidney homogenates. The results indicate that after peritubular removal, a small amount of insulin is degraded to form low-molecular-weight products similar to those seen with filtering kidneys and kidney homogenates. However, most of the insulin removed from the peritubular circulation is processed either to nonimmunoreactive products of molecular weight similar to that of insulin or, to a lesser extent, to products of larger molecular weight. Both these products are also formed by filtering kidneys. In the filtering kidney, the products having molecular weight similar to that of insulin probably originate from the peritubular process, because it is unlikely that material of this size could be derived from the filtration-absorption pathway. Of particular note was the finding that [125I]insulin trapped in the peritubular compartment of nonfiltering kidneys was displaced severalfold more effectively by unlabeled insulin than by several peptide hormones (P less than 0.01); the latter were no more effective than vehicle alone. The findings suggest the presence of peritubular insulin-specific receptors.

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.

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.

The effect of sodium iothalamate on the vascular resistance of the isolated perfused rat kidney

1991 ◽  
Vol 64 (757) ◽  
pp. 50-54 ◽  
Author(s):  
J. L. Haylor ◽  
A. A. El Sayed ◽  
A. M. EI Nahas ◽  
S. K. Morcos
Keyword(s):  
Vascular Resistance ◽  
Rat Kidney ◽  
Isolated Perfused Rat Kidney ◽  
Perfused Rat Kidney

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.

scholarly journals Effects of cyclosporine and its metabolites in the isolated perfused rat kidney.

1993 ◽  
Vol 4 (2) ◽  
pp. 168-177
Author(s):  
K A Roby ◽  
L M Shaw
Keyword(s):  
Vascular Resistance ◽  
Rat Kidney ◽  
Parent Drug ◽  
Renal Vascular Resistance ◽  
Isolated Perfused Rat Kidney ◽  
Perfused Rat Kidney ◽  
Before And After ◽  
Vascular Obstruction ◽  
Dose Responses ◽  
Renal Vascular

The isolated perfused rat kidney (IPK) was used to study the acute effects of cyclosporin A (CsA) and its metabolites (M1, M17, M18, M21 and M-COOH). GFR, renal vascular resistance, and sodium, potassium and water reabsorption were measured before and after the addition of CsA/metabolites/vehicles. There was no difference in CsA effect (mild decrease in GFR and increase in renal vascular resistance with the inclusion of plasma (10 mL) or whole blood (20 mL) in the albumin perfusate (120 mL). Intralipid was used as the vehicle for CsA and the metabolites because methanol, ethanol, and Cremophor had significant effects on GFR. Intralipid enhanced the effect of CsA 25-fold, giving CsA dose responses comparable to those of human kidneys. This enhanced effect with intralipid was due to vasoconstriction, not vascular obstruction, and was apparently specific to CsA (no enhancement of norepinephrine with Intralipid). The primary metabolites (M1, M17, and M21) caused decreases in GFR comparable to or slightly less than those caused by CsA. The secondary metabolites (M18 and M-COOH) caused more modest declines in GFR. Cyclosporine metabolite levels in patient blood often greatly exceed levels of the parent drug; these studies suggest that the metabolites may contribute significantly to CsA nephrotoxicity in patients.

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