Functional evaluation of isolated perfused rat kidney

1963 ◽  
Vol 18 (6) ◽  
pp. 1239-1246 ◽  
Author(s):  
Arthur W. Bauman ◽  
Thomas W. Clarkson ◽  
Ellen M. Miles
Keyword(s):  
Rat Kidney ◽  
Tubular Secretion ◽  
Functional Evaluation ◽  
Normal Limits ◽  
Glucose Reabsorption ◽  
Potassium Lactate ◽  
Perfused Rat Kidney ◽  
Filtered Load ◽  
Tubular Dilatation

A technique for perfusing the isolated rat kidney with heparinized whole blood is described. Numerous aspects of renal function are evaluated. Blood and urine flows approximated normal limits occasionally but diminished and increased, respectively, with time. The reabsorption rates of osmoles, sodium, chloride, potassium, lactate, and phosphate were proportional to the filtered loads. Variations in filtered load were due mainly to changes in glomerular filtration rate (GFR). Tubular secretion of p-amino hippuric acid varied with the GFR, and TmPAH per milliliter GFR was 60% of in vivo values. Glucose reabsorption was practically complete. Urine osmolalities, initially in the range 400–1,000 mosmoles/liter, fell during a perfusion, often to values well below plasma levels. Postperfusion histologic studies usually showed slight to moderate tubular dilatation. It was concluded that: 1) The handling of individual ions approximated in vivo function. 2) Changes in GFR and in the rate of excretion of PAH represented changes in the number of active nephrons. 3) Low urine osmolalities were due to decreasing ability of the nephrons to reabsorb water. blood and urine flow; electrolyte excretion Submitted on February 25, 1963

scholarly journals Metabolism of glycine- and hydroxyproline-containing peptides by the isolated perfused rat kidney

1985 ◽  
Vol 229 (2) ◽  
pp. 545-549 ◽  
Author(s):  
M Lowry ◽  
D E Hall ◽  
J T Brosnan
Keyword(s):  
Amino Acids ◽  
Rat Kidney ◽  
Isolated Perfused Rat Kidney ◽  
Perfused Rat Kidney ◽  
Rat Kidneys

Isolated perfused rat kidneys removed considerable quantities of glycyltyrosine, glycylhydroxyproline, tetraglycine and prolylhydroxyproline from the perfusate. The component amino acids are released into the perfusate and, in the case of the glycine-containing peptides, there is increased synthesis of serine. Removal of peptides was more than could be accounted for on the basis of filtration, so antiluminal metabolism is indicated. Metabolism of such peptides by the kidney may contribute to renal serine synthesis in vivo.

Acid excretion by bicarbonate-free perfused rat kidney

1981 ◽  
Vol 240 (4) ◽  
pp. F306-F310
Author(s):  
M. H. Garvey ◽  
D. L. Maude
Keyword(s):  
Carbonic Anhydrase ◽  
Rat Kidney ◽  
Acid Excretion ◽  
Total Acid ◽  
Urine Ph ◽  
Titratable Acid ◽  
Perfused Rat Kidney ◽  
Reduced Rate ◽  
Isolated Rat

We measured titratable acid (TA) and NH4 excretion by isolated rat kidneys perfused either with conventional bicarbonate-containing solutions or with solutions in which bicarbonate was replaced by propionate. Rates of TA excretion by bicarbonate-perfused kidneys were similar to in vivo values, 0.27 +/- 0.04 mueq.ml GF-1 (0.21 mueq.min-1.g-1), and increased significantly under bicarbonate-free conditions to 0.70 +/- 0.12 mueq.ml GF-1 (0.42 mueq.min-1.g-1). At the same time the perfusate/urine pH difference (delta pH) increased significantly, from 0.63 +/- 0.06 to 0.92 +/- 0.06. Carbonic anhydrase inhibition by 5 X 10(-4) M acetazolamide alkalinized the urine of bicarbonate-perfused kidneys, while in the bicarbonate-free preparation the urine remained acid (delta pH = 0.27 +/- 0.04) and titratable acid continued to be excreted, though at a reduced rate, 0.19 +/- 0.04 mueq.ml GF-1. Under these same bicarbonate-free carbonic anhydrase-inhibited conditions, lowering the perfusate pH from 7.4 to 7.1 increased delta pH to 0.36 +/- 0.02 and caused total acid excretion (TA + NH4) to rise from 0.29 +/- 0.04 to 0.45 +/- 0.06 mueq.ml GF-1, and increasing the perfusate [HPO4] from 2.4 to 9.6 mM increased TA to 0.80 +/- 0.09 mueq.ml GF-1.

Nitric oxide enhancement of erythropoietin production in the isolated perfused rat kidney

1995 ◽  
Vol 269 (4) ◽  
pp. C917-C922 ◽  
Author(s):  
K. Yoshioka ◽  
J. W. Fisher
Keyword(s):  
Nitric Oxide ◽  
Rat Kidney ◽  
Mrna Levels ◽  
Isolated Perfused Rat Kidney ◽  
Intracellular Cgmp ◽  
Perfused Rat Kidney ◽  
Arterial Po2

We have previously reported that nitric oxide (NO) and guanosine 3',5'-cyclic monophosphate (cGMP) may be involved in the regulation of erythropoietin (Epo) production in response to hypoxia both in vivo and in vitro (20). In the present studies, we have used the isolated perfused rat kidney to assess the role of NO in oxygen sensing and Epo production. When arterial PO2 was reduced from 100 mmHg (normoxemic) to 30 mmHg (hypoxemic) in the perfusate of this system, perfusate levels of Epo were significantly increased. This hypoxia-induced increase in Epo production was significantly decreased by the addition of NG-nitro-L-arginine methyl ester (L-NAME; 1 mM) to the perfusates. Hypoxemic perfusion also produced a significant increase, and L-NAME significantly inhibited this increase, in intracellular cGMP levels in the kidney when compared with normoxemic perfused kidneys. Quantitative reverse transcription-polymerase chain reaction also revealed that hypoxemic perfusion produced significant increases in Epo mRNA levels in the kidney, which was blocked by L-NAME. Our findings further support an important role for the NO/cGMP system in hypoxic regulation of Epo production.

Effects of atrial natriuretic peptides on metabolism of arginine vasopressin by isolated perfused rat kidney

1992 ◽  
Vol 263 (2) ◽  
pp. R273-R278
Author(s):  
M. R. Lebowitz ◽  
A. M. Moses ◽  
S. J. Scheinman
Keyword(s):  
Arginine Vasopressin ◽  
Rat Kidney ◽  
Fractional Excretion ◽  
Metabolic Clearance ◽  
Isolated Perfused Rat Kidney ◽  
Perfused Rat Kidney ◽  
Clearance Receptor ◽  
Atrial Natriuretic

Atrial natriuretic peptide (ANP) antagonizes the release and action of arginine vasopressin (AVP) both in vivo and in vitro. We have reported that ANP increases the urinary and metabolic clearances of AVP in normal subjects (A. M. Moses et al. J. Clin. Endocrinol. Metab. 70: 222-229, 1990). To clarify this effect, we perfused isolated rat kidneys in vitro and measured the clearances of AVP for 30 min after the addition of rat ANP [rANP-(1-28), 10(-7) M]. In the perfused kidney, rANP increased the urinary clearance of AVP (UCAVP) from 321 +/- 19 to 417 +/- 20 microliters/min (P less than 0.01) and increased the glomerular filtration rate (GFR) from 558 +/- 28 to 696 +/- 28 microliters/min (P less than 0.01). Fractional excretion of AVP was unchanged. Rates of AVP reabsorption were directly related to filtered AVP, and this relationship was not altered by ANP. ANP did not affect the total organ clearance or the renal metabolic clearance of AVP. The increase in GFR was associated with increases in renal vascular resistance (P less than 0.05), filtration fraction (P less than 0.01), and sodium excretion (P less than 0.001). UCAVP also increased when GFR was raised without ANP by perfusing at higher pressures. The rat ANP clearance receptor agonist [cANP- (4-23), 10(-7) M] did not change GFR or UCAVP. ANP increases UCAVP in the isolated perfused rat kidney. This appears to be a hemodynamic effect of ANP, acting through its biological receptor and not the clearance receptor.(ABSTRACT TRUNCATED AT 250 WORDS)

Cystine and lysine reabsorption in the isolated perfused rat kidney

1989 ◽  
Vol 256 (5) ◽  
pp. F901-F908
Author(s):  
K. A. Roby ◽  
S. Segal
Keyword(s):  
Transport System ◽  
Brush Border ◽  
Rat Kidney ◽  
Isolated Perfused Rat Kidney ◽  
Transport Studies ◽  
Perfused Rat Kidney ◽  
Renal Tubular Reabsorption ◽  
Renal Tubular

Renal tubular reabsorption of cystine and lysine were studied in the isolated perfused rat kidney to bridge the gap between in vivo clearance studies, and in vitro transport studies of tubule fragments, cells, and brush-border membranes. Lysine was reabsorped by a saturable transport system shared by the dibasics. Cystine was also reabsorbed by a saturable transport system, which was shared in part by the dibasics (maximum inhibition 30%). The lysine threshold (Fmin) was 0.9 mumol.min-1.g-1, with a tubular maximum (TM) of 2.4 mumol.min-1.g-1. The cystine Fmin was 0.06 mumol.min-1.g-1; the TM could not be estimated because it was above the limit of cystine solubility. There was no evidence of cystine ,secretion.- The gamma-glutamyltransferase inhibitor, AT-125, decreased cystine excretion, but only in the presence of glutathione, glycine, glutamate, and the diabasic amino acids. This suggests that cystine from glutathione degradation at the brush border may contribute to urinary cystine (an explanation of the phenomenon of cystine secretion), but only under certain conditions.

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.

Puromycin aminonucleoside nephrosis results in a marked increase in fractional clearance of albumin

1999 ◽  
Vol 277 (1) ◽  
pp. F139-F145 ◽  
Author(s):  
Tanya M. Osicka ◽  
Alexandra R. Hankin ◽  
Wayne D. Comper
Keyword(s):  
Rat Kidney ◽  
Tubular Epithelium ◽  
Size Selectivity ◽  
Puromycin Aminonucleoside ◽  
Glomerular Capillary Wall ◽  
Perfused Rat Kidney ◽  
Fractional Clearance ◽  
Aminonucleoside Nephrosis ◽  
Puromycin Aminonucleoside Nephrosis

Puromycin aminonucleoside nephrosis (PAN) results in a marked increase in the fractional clearance of albumin. The increase in the fractional clearance of [3H]albumin to ∼0.045, as measured both in vivo and in the isolated perfused rat kidney (IPK) with PAN, occurs without an accompanying equivalent increase in glomerular capillary wall size selectivity as previously measured with dextrans. This is very similar to the marked increase in albuminuria seen with kidneys treated with inhibitors of endocytosis by the tubular epithelium, particularly lysine (T. M. Osicka, L. M. Pratt, and W. D. Comper. Nephrology 2: 199–212, 1996). The similarity is further established that, like in the presence of lysine, [3H]albumin excreted in urine from rats with PAN is essentially intact whereas, in both in vivo and IPK control experiments, excreted [3H]albumin is heavily degraded. The same observations have also been made for3H-labeled anionic horseradish peroxidase. These observations suggest that the significant albuminuria that occurs in PAN is primarily post-glomerular basement membrane in origin.

Effect of cationic amino acid infusion on potassium metabolism in vivo

1964 ◽  
Vol 206 (2) ◽  
pp. 403-408 ◽  
Author(s):  
Herbert W. Dickerman ◽  
W. Gordon Walker
Keyword(s):  
Amino Acid ◽  
Tubular Secretion ◽  
Potassium Excretion ◽  
Acid Infusion ◽  
Cationic Amino Acid ◽  
Amino Acid Infusion ◽  
Cationic Amino Acids ◽  
K Secretion ◽  
Filtered Load

The infusion of the cationic amino l-lysine, l-arginine, or l-ornithine into dogs regularly increases potassium excretion to levels that exceed the filtered load of potassium. Hyperkalemia occurs during the amino acid infusion as a result of displacement of the intracellular potassium by the cationic amino acids. This rise in plasma K is not necessary for the stimulation of K secretion since infusion of the lysine directly into the renal artery produces K secretion without significant change in plasma K. This increased potassium excretion is promptly suppressed by the administration of thiomerin. The effects upon renal K handling in these experiments appear to be the result of facilitation of tubular secretion of K rather than inhibition of reabsorption.

Lactate increases potassium secretion by perfused rat kidney

1986 ◽  
Vol 251 (5) ◽  
pp. F873-F878
Author(s):  
M. Brezis ◽  
K. Spokes ◽  
P. Silva ◽  
F. H. Epstein
Keyword(s):  
Rat Kidney ◽  
Distal Tubule ◽  
Fractional Excretion ◽  
Metabolic Inhibitors ◽  
Metabolic Substrates ◽  
Fractional Excretion Of Sodium ◽  
Renal Oxygen Consumption ◽  
Perfused Rat Kidney ◽  
K Secretion

The effect of exogenous metabolic substrates on K+ secretion was evaluated in the isolated perfused rat kidney in the presence of 2-deoxyglucose and 2-tetradecylglycidic acid to inhibit utilization of glucose and fatty acids from endogenous sources. L-Lactate (15 mM) added to the perfusion medium enhanced renal oxygen consumption (4.0 +/- 1.1 mumol X min-1 X g-1 vs. 2.0 +/- 1.0 without lactate) while decreasing fractional excretion of sodium (19.3 +/- 2.4% vs. 47.3 +/- 1.8). L-Lactate markedly increased the fractional excretion of K+ to 181 +/- 29% compared with 68 +/- 12% without lactate (P less than 0.001). The poorly metabolized isomer D-lactate did not alter these parameters. The addition of alpha-ketoglutarate only slightly increased K+ excretion. In the absence of metabolic inhibitors and in the presence of glucose (5 mM), L-lactate also increased K+ excretion significantly more than did D-lactate (108 +/- 19% vs. 69 +/- 11, P less than 0.02). At the end of 90 min of perfusion with L-lactate medium, K+ concentration in the perfusate dropped from 4.7 +/- 0.05 to 3.2 +/- 0.2 meq/liter (vs. 3.8 +/- 0.1 meq/liter with D-lactate, P less than 0.005) without differences in glomerular filtration rate or sodium excretion. L-Lactate appears to increase K+ secretion by preferential metabolic stimulation of the distal tubule, a process that may help in vivo to prevent hyperkalemia in lactic acidosis.

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