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

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)

Download Full-text

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

AJP Cell Physiology ◽

10.1152/ajpcell.1995.269.4.c917 ◽

1995 ◽

Vol 269 (4) ◽

pp. C917-C922 ◽

Cited By ~ 10

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.

Download Full-text

Cystine and lysine reabsorption in the isolated perfused rat kidney

AJP Renal Physiology ◽

10.1152/ajprenal.1989.256.5.f901 ◽

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.

Download Full-text

Alterations of the renal function in the isolated perfused rat kidney system after in vivo and in vitro application of S-(1,2-dichlorovinyl)-L-cysteine and S-(2,2-dichlorovinyl)-L-cysteine

Archives of Toxicology ◽

10.1007/s002040050264 ◽

1996 ◽

Vol 70 (3-4) ◽

pp. 224-229 ◽

Cited By ~ 7

Author(s):

O. Ilinskaja ◽

S. Vamvakas

Keyword(s):

Renal Function ◽

Rat Kidney ◽

Isolated Perfused Rat Kidney ◽

Perfused Rat Kidney

Download Full-text

Comparison of the effects of parathyroid hormone (PTH) and recombinant PTH-related protein on bicarbonate excretion by the isolated perfused rat kidney

Journal of Endocrinology ◽

10.1677/joe.0.1260403 ◽

1990 ◽

Vol 126 (3) ◽

pp. 403-408 ◽

Cited By ~ 27

Author(s):

A. G. Ellis ◽

W. R. Adam ◽

T. J. Martin

Keyword(s):

Parathyroid Hormone ◽

Rat Kidney ◽

Urine Volume ◽

Clinical Manifestations ◽

Fractional Excretion ◽

Bicarbonate Concentration ◽

Isolated Perfused Rat Kidney ◽

Amino Terminal ◽

Fractional Excretion Of Sodium ◽

Perfused Rat Kidney

ABSTRACT The isolated perfused rat kidney was used to study the effects of amino-terminal fragments of human parathyroid hormone, hPTH(1–34), bovine parathyroid hormone, bPTH(1–84) and of PTH-related proteins, PTHrP(1–34), PTHrP(1–84), PTHrP(1–108) and PTHrP(1–141) on urinary bicarbonate excretion. PTHrP(1–34) (7 nmol/l), bPTH(1–84) (5·5 nmol/l) and hPTH(1–34) (7 nmol/l) had similar effects in increasing bicarbonate excretion with respect to the control. At lower concentrations (0·7 nmol/l) all PTHrP components, but not hPTH(1–34) or bPTH(1–84) increased bicarbonate excretion significantly. Infusions of PTHrP(1–108) and PTHrP(1–141) at 0·7 nmol/l, while associated with a rise in urinary bicarbonate concentration and excretion during the early stages of perfusion, produced a sharp decline in bicarbonate concentration and excretion in the latter part of perfusion. The different peptides produced no significant differences in glomerular filtration rate, fractional excretion of sodium or urine volume. The absence of substantial differences between the effects of hPTH(1–34) and PTHrP(1–34) are as noted in previous studies. The differences between PTHrP(1–108)/PTHrP(1–141) and PTHrP(1–34) demonstrated here are consistent with (1) the clinical manifestations of acidosis in hyperparathyroidism and alkalosis in humoral hypercalcaemia of malignancy, and (2) an independent action of a component of PTHrP beyond amino acids 1–34. Journal of Endocrinology (1990) 126, 403–408

Download Full-text

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

Biochemical Journal ◽

10.1042/bj2290545 ◽

1985 ◽

Vol 229 (2) ◽

pp. 545-549 ◽

Cited By ~ 7

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.

Download Full-text

Effect of epinephrine on renal potassium excretion in the isolated perfused rat kidney

AJP Renal Physiology ◽

10.1152/ajprenal.1984.247.2.f331 ◽

1984 ◽

Vol 247 (2) ◽

pp. F331-F338

Author(s):

L. D. Katz ◽

J. D'Avella ◽

R. A. DeFronzo

Keyword(s):

Rat Kidney ◽

Fractional Excretion ◽

Beta Agonist ◽

Potassium Excretion ◽

Isolated Perfused Rat Kidney ◽

Beta Agonists ◽

Beta Adrenergic Agonists ◽

Urinary Potassium ◽

Perfused Rat Kidney ◽

Renal Potassium Excretion

The effects of beta-agonists (epinephrine, isoproterenol, and ITP) and beta-antagonists (propranolol, metoprolol, and butoxamine) on renal potassium excretion were examined using the isolated perfused rat kidney preparation. Following 30 min of control perfusion, one of the above beta-adrenergic agonists or antagonists was added to the perfusion medium. Following epinephrine, a combined beta 1- and beta 2-agonist, urinary potassium excretion (UKV; 0.55 +/- 0.55 vs. 0.36 +/- 0.04 mueq/min, P less than 0.001) and fractional excretion of potassium (FEK; 24.6 +/- 2.4 vs. 18.2 +/- 2.0%, P less than 0.001) both decreased. When isoproterenol, a nonspecific beta-agonist, was added to the perfusate, UKV (0.49 +/- 0.10 vs. 0.27 +/- 0.04 mueq/min, P less than 0.02) and FEK (29.0 +/- 5.2 vs. 16.3 +/- 2.9%, P less than 0.01) again decreased. ITP, a specific beta 1-agonist also caused a decrease in UKV (0.60 +/- 0.13 vs. 0.39 +/- 0.04 mueq/min, P less than 0.02) and FEK (30.2 +/- 5.1 vs. 17.8 +/- 2.8%, P less than 0.02). In contrast, when propranolol, a nonspecific beta-antagonist, was added to the perfusate, the opposite effects on renal potassium handling were observed. UKV (0.45 +/- 0.05 vs. 0.70 +/- 0.07 mueq/min, P less than 0.001) and FEK (23.0 +/- 2.1 vs. 42.5 +/- 3.1%, P less than 0.001) both increased. Metoprolol (50 ng/ml), a specific beta 1-antagonist, increased UKV (0.56 +/- 0.10 vs. 0.68 +/- 0.15 mueq/min, P less than 0.02) and FEK (31.0 +/- 3.8 vs. 48.0 +/- 7.1%, P less than 0.02). A similar effect was observed when a higher dose of metoprolol (200 ng/ml) was employed.(ABSTRACT TRUNCATED AT 250 WORDS)

Download Full-text

Effect of vasoactive intestinal peptide on isolated perfused rat kidney

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1985.249.5.e494 ◽

1985 ◽

Vol 249 (5) ◽

pp. E494-E497 ◽

Cited By ~ 2

Author(s):

R. M. Rosa ◽

P. Silva ◽

J. S. Stoff ◽

F. H. Epstein

Keyword(s):

Vasoactive Intestinal Peptide ◽

Rat Kidney ◽

Urine Volume ◽

Fractional Excretion ◽

Rectal Gland ◽

Renal Nerves ◽

Isolated Perfused Rat Kidney ◽

Fractional Excretion Of Sodium ◽

Perfused Rat Kidney ◽

Renal Tubular

Vasoactive intestinal peptide, a polypeptide neurotransmitter, stimulates salt secretion by the mammalian intestine and the rectal gland of the dogfish shark. Because of the recent identification of vasoactive intestinal peptide in renal nerves, the present study was undertaken to investigate its effects on the isolated perfused rat kidney. The addition of vasoactive intestinal peptide to the recirculating perfusate produced a significant increase in urine volume, fractional excretion of sodium, chloride, and potassium, as well as osmolar clearance when compared with control kidneys. These changes associated with addition of vasoactive intestinal peptide occurred without any significant changes in perfusion flow, renal vascular resistance, or inulin clearance. These experiments strongly suggest an action of vasoactive intestinal peptide on renal tubular reabsorption.

Download Full-text

Renal Disposition of Colistin in the Isolated Perfused Rat Kidney

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00030-09 ◽

2009 ◽

Vol 53 (7) ◽

pp. 2857-2864 ◽

Cited By ~ 52

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.

Download Full-text