Renal Excretion of l-Epinephrine in the Dog

1958 ◽  
Vol 193 (2) ◽  
pp. 371-374 ◽  
Author(s):  
Richard T. Jones ◽  
William D. Blake

The renal excretion of epinephrine was studied in dogs anesthetized with sodium pentobarbital. Epinephrine in plasma and urine was quantitatively estimated by the fluorometric method of Lund. Glomerular filtration rate (creatinine clearance), renal plasma flow (PAH clearance) and PAH transport were employed as parameters of renal function. During periods of intravenous infusion of epinephrine, the percentage of hormone excreted was about 4.6% of that infused. The renal clearance of epinephrine was significantly greater than the glomerular filtration rate though less than renal plasma flow. From this and other information it was concluded that epinephrine is excreted both by tubular transport (tubular secretion) and glomerular filtration. The tubular transport of epinephrine was not inhibited by either 2,4-dinitrophenol or an adrenergic blocking agent.

Animals ◽  
2020 ◽  
Vol 10 (6) ◽  
pp. 1027
Author(s):  
Lenka Stroobant ◽  
Siska Croubels ◽  
Laura Dhondt ◽  
Joske Millecam ◽  
Siegrid De Baere ◽  
...  

The aim of the current study was to investigate the simultaneous measurement of plasma p-aminohippuric acid (PAH) clearance as a potential marker to assess effective renal plasma flow (eRPF) and tubular secretion (TS), and the plasma clearance of iohexol (IOH) as a marker of the glomerular filtration rate in poultry species. The PAH was administered intravenously (IV) to broiler chickens, layers, turkeys, Muscovy ducks, and pigeons. Each animal received successively a single bolus dose of 10 mg PAH/kg bodyweight (BW) and 100 mg PAH/kg BW to assess the eRPF and TS, respectively. Simultaneously with both PAH administrations, a single IV bolus of 64.7 mg/kg BW of IOH was administered. A high linear correlation (R2 = 0.79) between eRPF, based on the clearance of the low dose of PAH, and BW was observed for the poultry species. The correlation between TS, based on the clearance of the high dose of PAH, and BW was moderate (R2 = 0.50). Finally, a moderate correlation (R2 = 0.68) was demonstrated between GFR and eRPF and between GFR and TS (R2 = 0.56). This presented pharmacokinetic approach of the simultaneous administration of IOH and PAH enabled a simultaneous evaluation of eRPF/TS and GFR, respectively, in different poultry species.


2019 ◽  
Vol 104 (6) ◽  
pp. e28.1-e28
Author(s):  
L Dhondt ◽  
S Croubels ◽  
P De Paepe ◽  
P De Cock ◽  
M Devreese

BackgroundOver the years pigs were promoted as potential animal model for humans due to their high degree of anatomical and physiological similarities with humans. Gasthuys et al. demonstrated that the maturation of the kidney function in terms of the glomerular filtration rate (GFR) in growing pigs was comparable to humans, but no data are currently available on renal plasma flow, renal tubular secretion and reabsorption.1 The aim of this pilot study was to unravel the contribution of distinct renal elimination processes in juvenile pigs and to compare with reported human values.MethodsEight seven-week-old pigs were intravenously administered a single bolus of a cocktail of following renal markers: iohexol (64.7 mg/kg body weight (BW), GFR), para-aminohippuric acid (PAH, 10 mg/kg BW, effective renal plasma flow (ERPF) and anion secretion), pindolol (0.05 mg/kg BW, cation secretion) and fluconazole (0.5 mg/kg, tubular reabsorption). Plasma and urinary concentrations were determined for PAH, pindolol and fluconazole at several time points. Only plasma concentrations were assessed for iohexol. PK modelling was performed with Phoenix® WinNonlin®.ResultsThe clearance of iohexol was 97.9 ± 16.1 ml/min/m² (mean ± SD). The ERPF, calculated as the renal clearance of PAH, was 9.5 ± 2.1 ml/min/kg. These GFR and ERPF values are approximately a factor 1.3 higher than the values observed in humans, namely 63.5–75.0 mL/min/m² and 6.5 ± 2.0 mL/min/kg.2,3 The net tubular secretion of PAH was 5.4 ± 1.8 mL/min/kg, which was comparable with the values obtained in humans (5.0 ± 1.8 mL/min/kg).3 Results for cation secretion and tubular reabsorption are not yet available (to be presented at the congress).ConclusionThe net tubular secretion of PAH was comparable between the juvenile pigs and humans. The GFR and ERPF were generally a factor 1.3 higher in juvenile pigs compared to humans.ReferencesGasthuys E., et al., Postnatal maturation of the glomerular filtration rate in conventional growing piglets as potential juvenile animal model for preclinical pharmaceutical research. Frontiers in Pharmacology 2017. 8.Schwartz GJ, Furth SL. Glomerular filtration rate measurement and estimation in chronic kidney disease. Pediatric Nephrology 2007;22(11):1839–1848.Gross AS, et al., Simultaneous administration of a cocktail of markers to measure renal drug elimination pathways: absence of a pharmacokinetic interaction between fluconazole and sinistrin, p-aminohippuric acid and pindolol. British Journal of Clinical Pharmacology 2001. 51(6):547–555.Disclosure(s)This study was funded by the Special Research Fund of Ghent University (BOF16/DOC/285).


2020 ◽  
Vol 2 (5) ◽  
pp. 670-672
Author(s):  
Jesse C. Seegmiller ◽  
Brian J. Wolfe ◽  
Nansy Albtoush ◽  
Isabella Melena ◽  
Susan P. Gross ◽  
...  

1961 ◽  
Vol 200 (4) ◽  
pp. 878-880
Author(s):  
G. S. Kanter

Dogs were anesthetized with 30 mg/kg of sodium pentobarbital. Creatinine clearance was used as a measure of glomerular filtration rate and the clearance of p-aminohippuric acid at low plasma concentrations was used as a measure of renal plasma flow. After two control periods, the dogs were progressively hyperventilated. The respiratory minute volume was increased from about 4 l/min. at the start of the hyperventilation to about 8 l/min. at the end of 3 hours of overventilation. The anaerobically measured arterial pH rose from a control value of 7.33 to 7.63 at the conclusion of the experiment. No change occurred in the glomerular filtration rate, renal plasma flow, filtration fraction, hematocrit, rectal temperature, heart rate or total solids in the plasma. Passive hyperventilation leading to pronounced alkalosis of short duration does not appear to alter renal hemodynamics sufficiently to cause any change in the filtration rate or effective renal plasma flow.


1968 ◽  
Vol 48 (3) ◽  
pp. 487-508
Author(s):  
W. N. HOLMES ◽  
G. L. FLETCHER ◽  
D. J. STEWART

1. The renal excretion of water and electrolytes was examined in starved ducks maintained on fresh water and on hypertonic saline containing 284 mM/1. NaCl and 6.0 mM/l. KCl. 2. No significant differences were observed in the urine flow, glomerular filtration rate, renal plasma flow and the excretory rates of K+, NH4+ and inorganic phosphate between these two groups of birds. 3. The excretory rates of Na+, Cl- and Ca2+ were significantly higher in saline-maintained birds than in the freshwater-maintained birds. 4. NH4+ appeared to be a major cationic component which occupied over half of the available osmotic space in the urine of both the freshwater-maintained and saline-maintained birds. 5. In saline-maintained birds the excretion of K+ and inorganic phosphate appeared to be independent of the available osmotic space in the urine whereas the excretion of Na+ and Cl- appeared to be very dependent upon this factor. 6. These observations suggest that the kidneys of the saline-maintained bird constitute the primary pathway for the excretion of K+, NH4+ and inorganic phosphate, and that with respect to the excretion of Na+ they constitute a relatively minor pathway.


1956 ◽  
Vol 186 (1) ◽  
pp. 180-186 ◽  
Author(s):  
John E. Baer ◽  
Sue F. Paulson ◽  
Horace F. Russo ◽  
Karl H. Beyer

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.


1971 ◽  
Vol 10 (01) ◽  
pp. 16-24
Author(s):  
J. Fog Pedersen ◽  
M. Fog Pedersen ◽  
Paul Madsen

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.


1991 ◽  
Vol 81 (2) ◽  
pp. 271-279 ◽  
Author(s):  
P. G. McNally ◽  
F. Baker ◽  
N. Mistry ◽  
J. Walls ◽  
J. Feehally

1. Nifedipine ameliorates cyclosporin A-induced renal impairment in surgically intact (two-kidney) rats. This study investigates the effect of nifedipine on cyclosporin A nephrotoxicity in spontaneously hypertensive rats after either uninephrectomy or uninephrectomy with contralateral renal denervation. 2. Fourteen days after uninephrectomy pair-fed rats were injected for 14 days with cyclosporin A (25 mg/kg body weight) via the subcutaneous route and with nifedipine (0.1 mg/kg body weight) via the intraperitoneal route. Renal and systemic haemodynamics were measured in conscious unrestrained rats. 3. Whole-blood levels of cyclosporin A did not differ between groups (overall 352 ± 22 ng/ml, means ± sem). After uninephrectomy, cyclosporin A decreased the glomerular filtration rate (olive oil versus cyclosporin A: 0.96 ± 0.04 versus 0.70 ± 0.06 ml min−1 100 g body weight, P < 0.02) and effective renal plasma flow (1.94 ± 0.10 versus 1.38 ± 0.13, P < 0.01), and increased renal vascular resistance {(20.2 ± 1.8) × 104 versus (31.6 ± 3.3) × 104 kPa l−1 s [(20.2 ± 1.8) × 103 versus (31.6 ± 3.3) × 103 dyn s cm−5], P < 0.02} and mean arterial pressure (146.7 ± 6.7 versus 167.3 ± 2.9 mmHg, P < 0.05). Neither renal denervation nor nifedipine prevented the reduction in glomerular filtration rate or effective renal plasma flow induced by cyclosporin A. 4. This study infers that the sympathetic nervous system does not play an active role in cyclosporin A nephrotoxicity and demonstrates that the concomitant administration of nifedipine to rats with reduced renal mass does not ameliorate cyclosporin A-induced renal impairment.


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