Mechanism of leptin removal from the circulation by the kidney

1997 ◽  
Vol 155 (3) ◽  
pp. 577-585 ◽  
Author(s):  
F Cumin ◽  
HP Baum ◽  
N Levens
Keyword(s):  
Glomerular Filtration ◽  
Renal Plasma Flow ◽  
High Capacity ◽  
Renal Tubules ◽  
Primary Role ◽  
Sprague Dawley ◽  
Arterial Blood ◽  
Wide Range ◽  
Metabolic Degradation ◽  
Plasma Leptin

This study was performed to test the hypothesis that the kidneys play a primary role in the clearance of endogenous leptin from the circulation. Lean male Sprague-Dawley rats were anesthetized and subjected to various surgical manipulations of the kidneys. Sixty minutes after surgery arterial blood samples were taken at 1-h intervals for up to 8 h. Plasma leptin levels were determined by radioimmunoassay. Bilateral nephrectomy induced a rapid increase in plasma leptin concentrations above control values, indicating that the kidneys are important for the elimination of leptin from the circulation. Leptin was not metabolized across the renal circulation and was extracted intact by the kidney. Simultaneous measurement of renal plasma flow established renal leptin extraction at approximately 6.5 ng/min for both kidneys. Compared with the quantities extracted from the plasma, leptin was only present in the urine in small quantities, indicating extensive metabolic degradation in the renal tubules. High plasma leptin levels were not maintained after binephrectomy indicating that pathways other than the kidneys are also responsible for leptin clearance. Seven hours after bilateral ureteral ligation, a procedure which lowers glomerular filtration, plasma leptin levels were slightly elevated. The renal extraction of leptin did not change over a wide range of plasma leptin concentrations suggesting that renal leptin extraction is a high capacity, non-saturable process most probably glomerular filtration. Endogenous leptin is rapidly cleared from the circulation by glomerular filtration followed by metabolic degradation in the renal tubules.

Acute cyclosporine-induced renal vasoconstriction: lack of effect of theophylline

1990 ◽  
Vol 258 (1) ◽  
pp. F41-F45
Author(s):  
P. C. Churchill ◽  
N. F. Rossi ◽  
M. C. Churchill ◽  
A. K. Bidani ◽  
F. D. McDonald
Keyword(s):  
Renal Plasma Flow ◽  
Left Kidney ◽  
Chronic Administration ◽  
Sprague Dawley ◽  
Renal Vasoconstriction ◽  
Adenosine Receptor Antagonist ◽  
Arterial Blood ◽  
Sprague Dawley Rats ◽  
Group 1

Both acute and chronic administration of cyclosporine A (CSA) lead to renal vasoconstriction, but the mechanism is not fully understood. The present studies were designed to explore the possible role of adenosine in acute CSA-induced renal vasoconstriction in rats. Six groups of anesthetized Sprague-Dawley rats were studied using standard clearance techniques: group 1 rats were controls; groups 2, 4, and 6 received CSA intravenously at 20, 30, and 40 mg.h-1.kg body wt-1, respectively; groups 3 and 5 were identical to groups 2 and 4 except that a priming injection of theophylline was given (56 mumol/kg body wt) and theophylline was included in the intravenous infusate (0.56 mumol.min-1.kg body wt-1). CSA produced acute and concentration-dependent reductions in renal plasma flow (left kidney) and in the clearances of p-aminohippuric acid and inulin (both kidneys). Except in group 6, these changes were observed in the absence of a decrease in arterial blood pressure, demonstrating that CSA produced an acute and concentration-dependent increase in renovascular resistance. Theophylline not only failed to block CSA-induced renal vasoconstriction, if anything, it potentiated it. Because theophylline is an adenosine receptor antagonist, these findings contradict the hypothesis that adenosine mediates acute CSA-induced renal vasoconstriction.

scholarly journals Metabolic and Kinetic Considerations in the Use of [125I]HIPDM for Quantitative Measurement of Regional Cerebral Blood Flow

1985 ◽  
Vol 5 (1) ◽  
pp. 86-96 ◽  
Author(s):  
G. Lucignani ◽  
A. Nehlig ◽  
R. Blasberg ◽  
S. Patlak ◽  
L. Anderson ◽  
...  
Keyword(s):  
Time Course ◽  
Quantitative Measurement ◽  
Single Photon ◽  
Photon Emission ◽  
Sprague Dawley ◽  
Diffusion Limitations ◽  
Arterial Blood ◽  
Sprague Dawley Rats ◽  
Metabolic Products ◽  
Metabolic Degradation

The metabolic degradation and the kinetics of the cerebral uptake of N, N, N'-trimethyl- N'-(2-hydroxy-3-methyl- 5-[125I]iodobenzyl)-1, 3-propanediamine ([125I]HIPDM) have been studied in conscious, adult male Sprague-Dawley rats to determine its suitability as a tracer for the quantitative measurement of regional CBF (rCBF). rCBF was calculated by the indicator fractionation and the tissue equilibration methods in experiments of different durations up to 1 h. The values of rCBF obtained with [125I]HIPDM were compared with those obtained in concurrent measurements with [14C]iodoantipyrine in the same animals. Results of the experiments demonstrate that [125I]HIPDM is an inadequate tracer for use with the indicator fractionation method and that any method that employs [125I]HIPDM for the determination of rCBF must take into account its metabolic degradation, diffusion limitations, and bidirectional flux across the blood-brain barrier. With the tissue equilibration method, consistent determinations of rCBF may be possible with [125I]HIPDM by measurement of the time course of its concentration in arterial blood, corrected for the presence of 125I-labeled metabolic products, and its concentration in the brain at any time up to 1 h after its administration. The method may be adapted to measure rCBF in humans by means of single-photon emission tomography with [123I]HIPDM.

Systemic and renal haemodynamic changes in renal schemia/reperfusion injury: impact of erythropoietin

2012 ◽  
Vol 90 (11) ◽  
pp. 1535-1543 ◽  
Author(s):  
Abdel-Aziz M. Hussein ◽  
Nashwa Barakat ◽  
Amira Awadalla ◽  
Ahmed A. Shokeir
Keyword(s):  
Renal Function ◽  
Renal Plasma Flow ◽  
Treated Group ◽  
Significant Rise ◽  
Control Group ◽  
Sprague Dawley ◽  
Arterial Blood ◽  
Group I ◽  
Haemodynamic Changes ◽  
Renal Vascular

The objective of this study was to investigate the effects of erythropoietin (EPO) on systemic and renal hemodynamics in a rat model of renal ischemic/reperfusion (I/R) injury. We used 30 male Sprague–Dawley rats distributed among the following 3 groups (10 rats per group): (i) the sham-operated group, (ii) the control group (I/R injury only), and (iii) the EPO-treated group (I/R injury with 1500 U EPO·(kg body mass)–1 on day 0, and 500 U·kg–1 on days 2 and 4 after ischemia). Renal function, arterial blood pressure (ABP), renal plasma flow (RPF), renal blood flow (RBF), and renal vascular resistance (RVR) were measured on days 1, 2, and 7 after ischemia. The expression of endothelial NO synthase (eNOS) and histopathology of kidney were evaluated on day 7. The contractility of aortic strips was recorded from the different groups. The results show that renal function and histopathology were significantly improved after treatment with EPO. Compared with the control group, the EPO-treated group showed a significant increase in RPF, RBF, haematocrite, ABP, eNOS expression, and a decrease in RVR (p < 0.05).The response of aortic strips to the relaxant effect of acetylcholine was improved in the EPO-treated group. In conclusion, treatment with EPO improves renal function and renal haemodynamics in renal I/R injury, and causes significant rise of ABP and haematocrite value.

scholarly journals Nitric oxide: a potential mediator of amino acid-induced renal hyperemia and hyperfiltration.

1991 ◽  
Vol 1 (12) ◽  
pp. 1271-1277
Author(s):  
A J King ◽  
J L Troy ◽  
S Anderson ◽  
J R Neuringer ◽  
M Gunning ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Glomerular Filtration Rate ◽  
Amino Acid ◽  
Glomerular Filtration ◽  
Plasma Flow ◽  
Filtration Rate ◽  
Renal Plasma Flow ◽  
Competitive Inhibitor ◽  
Arterial Blood

The role of nitric oxide in the modulation of systemic and renal hemodynamics was examined by using N omega-monomethyl-L-arginine (L-NMMA, 110 micrograms/kg/min), a competitive inhibitor of the conversion of L-arginine to nitric oxide. L-NMMA or saline vehicle (9.6 microL/min) was infused intravenously into anesthetized euvolemic Munich-Wistar rats. After 30 min, L-NMMA resulted in a uniform increase in mean arterial blood pressure (111 +/- 1 to 128 +/- 2 mmHg; P less than 0.05) and a modest reduction in renal plasma flow rate (4.4 +/- 0.2 to 4.2 +/- 0.1 mL/min; P less than 0.05), without change in glomerular filtration rate (1.16 +/- 0.03 to 1.15 +/- 0.03 mL/min); vehicle had no effect on these renal parameters. These rats were then subdivided to receive an intravenous infusion (37 microL/min) of either 10% glycine, 11.4% mixed amino acids, or equiosmolar dextrose. L-NMMA pretreatment markedly attenuated glycine-induced hyperfiltration (10 +/- 6 versus 33 +/- 5%, L-NMMA versus vehicle; P less than 0.05) and obliterated the renal hyperemic response (-7 +/- 6 versus 16 +/- 4%, L-NMMA versus vehicle; P less than 0.05). L-NMMA also caused modest blunting of the mixed amino acid-induced hyperfiltration (18 +/- 4 versus 30 +/- 4%, L-NMMA versus vehicle; P = 0.056) but failed to curtail the renal hyperemia (16 +/- 6 versus 20 +/- 4%). Dextrose had no effect on glomerular filtration rate or renal plasma flow.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of Serotonin on Renal Hemodynamics and Sodium Excretion in the Dog

1958 ◽  
Vol 193 (3) ◽  
pp. 639-643 ◽  
Author(s):  
William P. Blackmore
Keyword(s):  
Glomerular Filtration Rate ◽  
Glomerular Filtration ◽  
Plasma Flow ◽  
Sodium Excretion ◽  
Filtration Rate ◽  
Direct Action ◽  
Renal Plasma Flow ◽  
Specific Effect ◽  
Arterial Blood ◽  
Change In Mean

The effects of constant intravenous infusion of serotonin with doses of 5 and 10 µg/kg/min. on glomerular filtration rate, effective renal plasma flow, urine flow and sodium excretion were studied in trained, unanesthetized female dogs. A small but significant decrease in glomerular filtration rate associated with increased renal plasma flow occurred at the 5 µg/kg/min. dose indicating a specific effect of serotonin on the kidney. Similar changes were noted with the 10 µg/kg/min. dose plus a marked antidiuretic effect that occurred in the absence of any significant change in mean arterial blood pressure and an intact neurohypophysis indicating a direct action on water reabsorption in the kidney. Urinary sodium excretion decreased with both doses as a result of a decline in glomerular filtration rate associated with increased tubular reabsorption. These results indicate that serotonin has a specific effect on the kidney and suggest that this substance may alter the caliber of the glomerular vessels to decrease renal vascular resistance.

The Effects of Vandellia Cordifolia on Renal Functions and Arterial Blood Pressure

1989 ◽  
Vol 17 (03n04) ◽  
pp. 203-210
Author(s):  
Huei-Yann Tsai ◽  
Ruey-Tean Chiang ◽  
Tzu-Wei Tan ◽  
Ho-Chan Chen
Keyword(s):  
Blood Pressure ◽  
Blood Flow ◽  
Glomerular Filtration Rate ◽  
Glomerular Filtration ◽  
Renal Blood Flow ◽  
Filtration Rate ◽  
Renal Tubules ◽  
Diuretic Effect ◽  
Renal Functions ◽  
Arterial Blood

Vandellia cordifolia (COLSM) G, DON of Scrophulariaceae (V. cordifolia) is an annual wild herb indigenous to Taiwan. It can be found in plains, low altitudes, swampy places, and paddy fields. Taiwanese folk physicians use it in "nephritis, uremia, furnucle, carbuncle." The LD50 (95% confidence limit) of the crude exract of V. codifolia given by the oral route was more than 10 g/kg in rats. By the intraperitoneal route, it was 4.6 g/kg (4.35–4.93), The extraction rate was 16.6%. We studied its effects on renal functions and blood pressure and found that (1) it had diuretic effect on normal rats, (2) it decreased glomerular filtration rate and renal blood flow on normal kidneys in rabbits, (3) it had no effects on glomerular filtration rate and renal blood flow on glycerin-induced insufficient kidneys in rabbits, (4) it had diuretic effects on both normal and glycerin-induced insufficient kidneys in rabbits, (5) it could inhibit Na+ and K+ reabsorptionn on normal and glycerin-induced insufficient kidneys in rabbits, (6) it had hypertensive effect and this effect could be blocked by phenoxybenzamine. From the above facts, we conclude that V, cordifolia had diuretic effect and it may act on renal tubules to inhibit Na+ and K+ reabsorption.

Cardiovascular, endocrine, and renal effects of urodilatin in normal humans

1999 ◽  
Vol 276 (3) ◽  
pp. R684-R695 ◽  
Author(s):  
Morten Heiberg Bestle ◽  
Niels Vidiendal Olsen ◽  
Poul Christensen ◽  
Benny Vittrup Jensen ◽  
Peter Bie
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Cardiac Output ◽  
Glomerular Filtration Rate ◽  
Stroke Volume ◽  
Glomerular Filtration ◽  
Filtration Rate ◽  
Excretion Rate ◽  
Renal Tubules ◽  
Arterial Blood

Effects of urodilatin (5, 10, 20, and 40 ng ⋅ kg−1⋅ min−1) infused over 2 h on separate study days were studied in eight normal subjects with use of a randomized, double-blind protocol. All doses decreased renal plasma flow (hippurate clearance, 13–37%) and increased fractional Li+clearance (7–22%) and urinary Na+excretion (by 30, 76, 136, and 99% at 5, 10, 20, and 40 ng ⋅ kg−1⋅ min−1, respectively). Glomerular filtration rate did not increase significantly with any dose. The two lowest doses decreased cardiac output (7 and 16%) and stroke volume (10 and 20%) without changing mean arterial blood pressure and heart rate. The two highest doses elicited larger decreases in stroke volume (17 and 21%) but also decreased blood pressure (6 and 14%) and increased heart rate (15 and 38%), such that cardiac output remained unchanged. Hematocrit and plasma protein concentration increased with the three highest doses. The renin-angiotensin-aldosterone system was inhibited by the three lowest doses but activated by the hypotensive dose of 40 ng ⋅ kg−1⋅ min−1. Plasma vasopressin increased by factors of up to 5 during infusion of the three highest doses. Atrial natriuretic peptide immunoreactivity (including urodilatin) and plasma cGMP increased dose dependently. The urinary excretion rate of albumin was elevated up to 15-fold (37 ± 17 μg/min). Use of a newly developed assay revealed that baseline urinary urodilatin excretion rate was low (<10 pg/min) and that fractional excretion of urodilatin remained below 0.1%. The results indicate that even moderately natriuretic doses of urodilatin exert protracted effects on systemic hemodynamic, endocrine, and renal functions, including decreases in cardiac output and renal blood flow, without changes in arterial pressure or glomerular filtration rate, and that filtered urodilatin is almost completely removed by the renal tubules.

HAEMODYNAMIC STUDIES IN MAN BEFORE AND AFTER HYPOPHYSECTOMY

1962 ◽  
Vol 39 (2) ◽  
pp. 308-322 ◽  
Author(s):  
Göran Bojs ◽  
Thomas Falkheden ◽  
Björn Sjögren ◽  
Edvardas Varnauskas
Keyword(s):  
Cardiac Output ◽  
Oxygen Consumption ◽  
Glomerular Filtration Rate ◽  
Glomerular Filtration ◽  
Plasma Flow ◽  
Filtration Rate ◽  
Renal Plasma Flow ◽  
Arterial Blood ◽  
Chromophobe Adenoma ◽  
Before And After

ABSTRACT Determinations of cardiac output and oxygen consumption simultaneously with measurements of glomerular filtration rate and renal plasma flow were performed before and after hypophysectomy in two cases of acromegaly, two cases of metastatic mammary carcinoma, one case of diabetes mellitus and in one case of chromophobe adenoma. After hypophysectomy evidence of adrenocortical insufficiency was present in all but one subject and these patients were on substitution therapy with cortisone (17,21-dihydroxy-pregn-4-ene 3,11,20-trione) at the time of the postoperative studies. In two patients at least, postoperative hypothyroidism could not be demonstrated. In all cases, however, hypophysectomy was followed by a marked and roughly parallel reduction in cardiac output and oxygen consumption. A substantial decrease in glomerular filtration rate, renal plasma flow and renal blood flow following hypophysectomy was also found while no or only slight changes in mean brachial arterial blood pressure were observed. The changes in renal function did not always parallel the reduction in cardiac output.

Renal Elimination of 3-Methylaminoisocamphane Hydrochloride (Mecamylamine)

1956 ◽  
Vol 186 (1) ◽  
pp. 180-186 ◽  
Author(s):  
John E. Baer ◽  
Sue F. Paulson ◽  
Horace F. Russo ◽  
Karl H. Beyer
Keyword(s):  
Glomerular Filtration Rate ◽  
Gastrointestinal Tract ◽  
Glomerular Filtration ◽  
Plasma Flow ◽  
Filtration Rate ◽  
Renal Plasma Flow ◽  
Tubular Secretion ◽  
Renal Elimination ◽  
Renal Tubules ◽  
Extraction Study

Mecamylamine, 3-methylaminoisocamphane hydrochloride, a secondary amine with a pka of 11.4, can be both actively secreted and actively reabsorbed by the renal tubules in the dog. Net secretion occurs when the urine is acid; net reabsorption occurs when the urine is alkaline. A direct renal extraction study showed that tubular secretion occurred at rates equal to effective renal plasma flow. No self-depression of tubular secretion was observed at increased loads. The clearance of mecamylamine was depressed below glomerular filtration rate when the urine became alkaline, whether or not a systemic alkalosis existed. In some experiments, the clearance was as low as 3 ml/min., corresponding to reabsorption of more than 90% of the filtered drug. The secretory mechanism is not identical with that for p-aminohippurate. Approximately one-fourth of an administered dose of mecamylamine is excreted in the urine within 24 hours, whether the drug is given orally or parenterally. These data are consistent with the biological evidence that absorption from the gastrointestinal tract is essentially complete, and that extrarenal factors are important in the over-all physiological economy of the drug.

Clinical Renal Function Testing by External Double Isotope Monitoring Technique

1971 ◽  
Vol 10 (01) ◽  
pp. 16-24
Author(s):  
J. Fog Pedersen ◽  
M. Fog Pedersen ◽  
Paul Madsen
Keyword(s):  
Renal Function ◽  
Glomerular Filtration Rate ◽  
Glomerular Filtration ◽  
Plasma Flow ◽  
Filtration Rate ◽  
Renal Plasma Flow ◽  
Correlation Coefficients ◽  
Feedback System ◽  
Effective Renal Plasma Flow ◽  
Advantages And Disadvantages

SummaryAn accurate catheter-free technique for clinical determination simultaneouslyof glomerular filtration rate and effective renal plasma flow by means of radioisotopes has been developed. The renal function is estimated by the amount of radioisotopes necessary to maintain a constant concentration in the patient’s blood. The infusion pumps are steered by a feedback system, the pumps being automatically turned on when the radiation measured over the patient’s head falls below a certain preset level and turned off when this level is again readied. 131I-iodopyracet was used for the estimation of effective renal plasma flow and125I-iothalamate estimation of the glomerular filtration rate. These clearances were compared to the conventional bladder clearances and good correlation was found between these two clearance methods (correlation coefficients 0.97 and.90 respectively). The advantages and disadvantages of this new clearance technique are discussed.

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