Urine Electrolyte Response to 18-Hydroxy-11-Deoxycorticosterone in Normal Man

1977 ◽  
Vol 53 (5) ◽  
pp. 493-498 ◽  
Author(s):  
M. G. Nicholls ◽  
R. Fraser ◽  
G. Hay ◽  
P. Mason ◽  
B. Torsney
Keyword(s):  
Marked Effect ◽  
Plasma Concentrations ◽  
Urine Volume ◽  
Metabolic Clearance ◽  
Potassium Excretion ◽  
Metabolic Clearance Rate ◽  
Urine Ph ◽  
Urine Potassium ◽  
Normal Man ◽  
Plasma Half Life

1. To assess whether the adrenal corticosteroid 18-hydroxy-11-deoxycorticosterone [18-(OH)DOC] affects urine electrolyte excretion in normal man, seven male volunteers received 120 μg (353 nmol) intravenously in 1 h. This was compared with glucose (50 g/l; control) and aldosterone (80 μg, 222 nmol) infusions in the same subjects. 2. A definite though weak antinatriuretic response to 18-(OH)DOC was observed, whereas urine potassium excretion was not altered. Aldosterone increased urine potassium excretion and reduced sodium output. Urine pH was lowered by both corticosteroids, aldosterone in general having a more marked effect. Urine volume was not altered by 18-(OH)DOC. 3. Plasma concentrations of 18-(OH)DOC and aldosterone rose approximately tenfold during their respective infusions. Compared with that of aldosterone, the metabolic clearance rate of 18-(OH)DOC was slower and its plasma half-life was longer. 4. We have been able to demonstrate that 18-(OH)DOC has a definite, albeit weak antinatriuretic action in normal man, but whether or not this corticosteroid is capable of elevating the blood pressure in man remains to be shown.

Comparative metabolic clearance rate, volume of distribution and plasma half-life of human β-lipotropin and acth

Life Sciences ◽  
1978 ◽  
Vol 23 (23) ◽  
pp. 2323-2330 ◽  
Author(s):  
Anthony S. Liotta ◽  
Choh Hao Li ◽  
George C. Schussler ◽  
Dorothy T. Krieger
Keyword(s):  
Clearance Rate ◽  
Half Life ◽  
Volume Of Distribution ◽  
Metabolic Clearance ◽  
Metabolic Clearance Rate ◽  
Plasma Half Life

Excretion of progastrin products in human urine

1999 ◽  
Vol 276 (4) ◽  
pp. G985-G992 ◽  
Author(s):  
C. Palnaes Hansen ◽  
J. P. Goetze ◽  
F. Stadil ◽  
J. F. Rehfeld
Keyword(s):  
Glomerular Filtration Rate ◽  
Glomerular Filtration ◽  
Filtration Rate ◽  
Plasma Concentrations ◽  
Metabolic Clearance ◽  
Metabolic Clearance Rate ◽  
Renal Handling ◽  
Renal Metabolism ◽  
Tubular Transport ◽  
Excretion Rates

The renal handling of carboxyamidated gastrins, NH2-terminal progastrin fragments, and glycine-extended gastrins was examined in healthy volunteers. The respective urinary clearances after a meal amounted to 0.09 ± 0.02%, 0.17 ± 0.04% ( P< 0.05), and 0.04 ± 0.01% ( P< 0.01) of the glomerular filtration rate. During intravenous infusion of carboxyamidated gastrin-17, progastrin fragment-(1—35), and glycine-extended gastrin-17, the respective urinary clearances amounted to 0.08 ± 0.02, 0.46 ± 0.08, and 0.02 ± 0.01%, respectively, of the glomerular filtration rate. The metabolic clearance rate of the three peptides was 24.4 ± 1.3, 6.0 ± 0.4, and 8.6 ± 0.7 ml ⋅ kg−1⋅ min−1. A maximum rate for tubular transport or degradation of the peptides could not be determined, nor was a renal plasma threshold recorded. Plasma concentrations and urinary excretion rates correlated for gastrin-17 and progastrin fragment-(1—35) ( r = 0.94 and 0.97, P < 0.001), whereas the excretion of glycine-extended gastrin diminished with increasing plasma concentrations. We conclude that renal excretion of progastrin products is negligible compared with renal metabolism and that renal handling of the peptides depends on their molecular structure. Hence, the kidneys exhibited a higher excretion of NH2-terminal progastrin fragments than of carboxyamidated and especially glycine-extended gastrins.

Comparative Bioactivity of Atrial and Brain Natriuretic Peptides in An Ovine Model of Heart Failure

1997 ◽  
Vol 92 (2) ◽  
pp. 159-165 ◽  
Author(s):  
Miriam Tessa Rademaker ◽  
Christopher John Charles ◽  
Eric Arnold Espiner ◽  
Christopher Miles Frampton ◽  
Michael Gary Nicholls ◽  
...  
Keyword(s):  
Heart Failure ◽  
Natriuretic Peptide ◽  
Urine Volume ◽  
Peripheral Resistance ◽  
Pressure Control ◽  
Guanosine Monophosphate ◽  
Metabolic Clearance ◽  
Ovine Model ◽  
Metabolic Clearance Rate ◽  
Brain Natriuretic Peptides

1. Whereas many studies have detailed the effects of exogenous atrial natriuretic peptide (ANP) infusions in heart failure, and a limited number have examined the effects of brain natriuretic peptide (BNP), none have directly compared the bioactivity of similar doses of ANP and BNP under standard conditions of impaired cardiac function. We compared the hormonal, haemodynamic and renal effects of 3 h infusions of ANP, BNP and a vehicle control in eight sheep with pacing-induced heart failure (225 beats/min for 8–12 days). 2. Infusion of ANP and BNP increased plasma ANP (P < 0.001) (276 ± 27 versus control 142 ± 26 pmol/l) and BNP (P < 0.001) (257 ± 34 versus control 45 ± 5 pmol/l) respectively, in association with increased cyclic 3′,5′-guanosine monophosphate [control, 40 ± 6; ANP, 53 ± 6 (P < 0.05); BNP, 57 ± 7 nmol/l (P < 0.001)]. Metabolic clearance rate and half-life were similar for both peptides. Infusion of ANP and BNP similarly reduced mean arterial pressure [control, 73.0 ± 1.6; ANP, 67.6 ± 1.2 (P < 0.01); BNP, 65.7 ± 1.7 mmHg (P < 0.001)], left atrial pressure (both P < 0.05) (control, 22.0 ± 0.7; ANP, 19.9 ± 1.0; BNP, 19.8 ± 0.9 mmHg) and peripheral resistance [control, 50.3 ± 4.1 mmHg l−1 min−1; ANP, 46.0 ± 2.8 (P < 0.05); BNP, 43.8 ± 4.5 (P < 0.01)], and increased urine volume (2-3-fold, both P < 0.05), sodium excretion (> 10-fold, both P < 0.01) and haematocrit levels relative to control (both P < 0.05). Infused BNP tended to raise plasma ANP levels (by 28 pmol/l), while ANP increased plasma BNP (by 18 pmol/l). Plasma aldosterone was reduced by approximately 40% by both peptides (both P < 0.05). 3. In conclusion, ANP and BNP are both powerfully natriuretic, similarly suppress aldosterone and appear equipotent in reducing preload and after-load in this model of pacing-induced heart failure.

Assessment of Glucose Turnover in Normal Man with the Use of a Non-Radioactive Isotopically Labelled Preparation, [6,6-2H]Glucose, as Tracer

1982 ◽  
Vol 63 (5) ◽  
pp. 437-440 ◽  
Author(s):  
J. W. Haigh ◽  
D. G. Johnston ◽  
A. J. McCulloch ◽  
M. F. Laker ◽  
J. Welby ◽  
...  
Keyword(s):  
Gas Chromatography Mass Spectrometry ◽  
Glucose Turnover ◽  
Metabolic Clearance ◽  
Intravenous Bolus ◽  
Metabolic Clearance Rate ◽  
Glucose Kinetics ◽  
Radioactive Label ◽  
Normal Man ◽  
The Mean ◽  
Male Subjects

1. Glucose kinetics were assessed in seven normal adult male subjects by an intravenous bolus technique with the use of a non-radioactive isotopically labelled preparation, [6,6-2H]glucose, as tracer. Tracer enrichment in plasma was assessed by gas chromatography-mass spectrometry. For comparison five subjects also received a simultaneous intravenous bolus of [6-3H]glucose and kinetics were assessed by conventional means. 2. Administration of [6,6-2H]glucose did not alter circulating glucose or insulin concentrations. 3. Glucose turnover, assessed by the use of [6,6-2H]glucose, was 11·4 (±0·9) μmol min−1 kg−1 and 11·6 (±0·5) μmol min−1 kg−1 with [6-3H]glucose. The mean metabolic clearance rate of glucose was 2·3 (±0·3) ml min−1 kg−1 with both isotopically labelled tracers. Estimates of mean residence time, glucose pool and glucose space were also similar by each technique. 4. [6,6-2H]Glucose is therefore an effective tracer and allows investigation of glucose kinetics without administration of a radioactive label.

Metabolic clearance rate in sheep of a met-enkephalin analogue estimated by radioimmunoassay

1982 ◽  
Vol 93 (3) ◽  
pp. 427-433 ◽  
Author(s):  
J. E. Bolton ◽  
J. H. Livesey ◽  
R. A. Donald
Keyword(s):  
Clearance Rate ◽  
Bolus Injection ◽  
Plasma Concentrations ◽  
Volume Of Distribution ◽  
Metabolic Clearance ◽  
Metabolic Clearance Rate ◽  
Time Intervals ◽  
Naturally Occurring ◽  
Specific Radioimmunoassay ◽  
The Mean

A sensitive and specific radioimmunoassay developed for measuring the met-enkephalin analogue d-ala2-met(0)5-ol-enkephalin (DAMME) was used to study the pharmacokinetics of DAMME in the circulation of sheep. Plasma concentrations of DAMME were measured at varying time-intervals after an intravenous bolus injection or following a constant intravenous infusion of the analogue. The mean metabolic clearance rate of DAMME was 2·8 ml/min per kg, the mean circulating half-life was 52 min and the mean volume of distribution was 190 ml/kg. The longer circulating time of the analogue when compared with that of naturally occurring met-enkephalin would appear to explain its prolonged analgesic effect.

Aldosterone metabolism in isolated perfused rat kidney.

1978 ◽  
Vol 234 (5) ◽  
pp. E472
Author(s):  
H Nakane ◽  
Y Nakane ◽  
G Reach ◽  
P Corvol ◽  
J Menard
Keyword(s):  
Urinary Excretion ◽  
Perfusion Pressure ◽  
Rat Kidney ◽  
Urine Volume ◽  
Metabolic Clearance ◽  
Metabolic Clearance Rate ◽  
Renal Metabolism ◽  
Isolated Perfused Rat Kidney ◽  
Perfused Rat Kidney ◽  
Acid Labile

The renal metabolism and handling of [1,2-3H]aldosterone ([3H]A) was studied using isolated perfused rat kidney under different perfusion conditions. The metabolite production rate (MPR) and the urinary excretion of [3H]A together with its radiometabolites (UV/P3H) were studied. Among the formed metabolites, no acid-labile conjugate of aldosterone (ALC) was detected. The MPR was not altered in studies using nonfiltering kidney, a result that suggests that the majority of metabolites were formed without requirement of the process of glomerular filtration and tubular uptake of the hormone. High perfusion pressure (high PP) resulted in a striking increase in whole metabolic clearance rate of aldosterone (MCR[3H]A) due mostly to an enhanced urinary excretion of intact aldosterone and, to a lesser degree, to a significant increase in MPR. Factors determining the excretion rate of [3H]A and its metabolites were than investigated under administration of diuretics. Mannitol (44 mM) induced a marked increase in urine volume (UV) accompanied by a significant UV/P3H increase. Meanwhile, 0.1 mM furosemide resulted in an increase only in UV, but not in UV/P3H. These results revealed the UV dependence of aldosterone excretion in certain diuretic conditions.

Metabolic clearance rate of arginine vasopressin in severe chronic renal failure

1992 ◽  
Vol 83 (5) ◽  
pp. 583-587 ◽  
Author(s):  
Nicholas B. Argent ◽  
Robert Wilkinson ◽  
Peter H. Baylis
Keyword(s):  
Renal Failure ◽  
Steady State ◽  
Chronic Renal Failure ◽  
Arginine Vasopressin ◽  
Clearance Rate ◽  
Plasma Concentrations ◽  
Normal Subjects ◽  
Metabolic Clearance ◽  
Metabolic Clearance Rate ◽  
Plasma Arginine

1. The metabolic clearance rate of arginine vasopressin was determined using a constant infusion technique in normal subjects and patients with chronic renal failure immediately before commencing dialysis. Endogenous arginine vasopressin was suppressed in all subjects before the infusion with a water load. 2. Plasma arginine vasopressin concentrations were determined using a sensitive and specific radioimmunoassay after Florisil extraction. The detection limit of the assay was 0.3 pmol/l, and intra- and inter-assay coefficients of variation at 2 pmol/l were 9.7% and 15.3%, respectively. 3. In normal subjects, the metabolic clearance rate was determined at two infusion rates producing steady-state concentrations of arginine vasopressin of 1.3 and 4.4 pmol/l. In the patients with renal failure, a single infusion rate was used, producing a steady-state concentration of 1.5 pmol/l. 4. At comparable plasma arginine vasopressin concentrations, metabolic clearance rate was significantly reduced in patients with renal failure (normal 1168 ± 235 ml/min versus renal failure 584 ± 169 ml/min; means ± sd; P<0.001). 5. Free water clearance was significantly reduced in normal subjects during the arginine vasopressin infusion from 8.19 ± 2.61 to −1.41 ± 0.51 ml/min (P<0.001), but was unchanged in the patients with renal failure after attaining comparable plasma arginine vasopressin concentrations. 6. In normal subjects there was a small but significant fall in metabolic clearance rate at the higher steady-state arginine vasopressin concentration (1168 ± 235 ml/min at 1.3 pmol/l versus 1059 ± 269 ml/min at 4.4 pmol/l; P = 0.016). 7. Our results show that the metabolic clearance rate of arginine vasopressin is reduced by approximately 50% in severe chronic renal failure. This alone may account for the raised plasma concentrations of the hormone seen in this condition.

scholarly journals The effects on glucose metabolism of feeding a high-urea diet to sheep

1977 ◽  
Vol 38 (3) ◽  
pp. 455-462 ◽  
Author(s):  
M. C. Leonard ◽  
P. J. Buttery ◽  
D. Lewis
Keyword(s):  
Glucose Metabolism ◽  
Crude Protein ◽  
Plasma Concentrations ◽  
Basal Diet ◽  
Metabolic Clearance ◽  
Crude Protein Content ◽  
Metabolic Clearance Rate ◽  
Protein Nitrogen ◽  
Urea Treatment ◽  
Alternative Diet

1. Sheep were given either a basal diet of 107 g crude protein (nitrogen × 6.25)/kg or the same diet to which urea was added to increase the crude protein content to 221 g/kg. Isotope-dilution techniques with [U-14C]glucose and [2-3H]glucose were used to measure various criteria of glucose metabolism. The plasma concentrations of urea and potassium were determined. The sheep were then given the alternative diet and the experiment was repeated.2. Plasma K concentrations were decreased on feeding urea (P < 0.05).3. Plasma glucose concentrations were reduced on the urea treatment (P < 0.05), while glucose space and metabolic clearance rate were not significantly reduced (P > 0.05).4. Some implications for the feeding of non-protein-N to ruminants are discussed.

Hyperinsulinemia of obesity is due to decreased clearance of insulin

1983 ◽  
Vol 245 (2) ◽  
pp. E155-E159 ◽  
Author(s):  
M. T. Meistas ◽  
S. Margolis ◽  
A. A. Kowarski
Keyword(s):  
Plasma Concentrations ◽  
Hepatic Clearance ◽  
Normal Activity ◽  
Metabolic Clearance ◽  
Metabolic Clearance Rate ◽  
Equimolar Ratio ◽  
Secretory Rate ◽  
C Peptide ◽  
Constant Rate ◽  
Obese Subjects

The hyperinsulinemia of obesity could result from a decrease in the metabolic clearance rate of insulin (MCR-I), an increase in the secretory rate of insulin (SR-I), or a combination of both these processes. Because C-peptide and insulin are secreted in an equimolar ratio, the plasma concentrations of C-peptide (C) and insulin (I) are inversely proportional to their rates of metabolic clearance (C/I = MCR-I/MCR-C). We obtained 24-h integrated concentrations (IC) of insulin (IC-I) and C-peptide (IC-C) in 23 obese and 45 nonobese subjects over a period of normal activity and food intake. The IC-I was 69% higher in the obese subjects (P less than 0.0001). A 13% increase in the IC-C (P = 0.04), with a constant rate of C-peptide clearance, indicates a proportionate increase in SR-I. A 33% decrease in the IC-C/IC-I in the obese group (P less than 0.005) reflects a decrease in MCR-I; hence, 75% of the hyperinsulinemia is due to a decrease in the clearance of insulin. Because peripheral MCR-I (pMCR-I) is similar in obese and nonobese subjects, the decrease in MCR-I may be due to a decrease in the hepatic clearance of insulin. This conclusion was supported by our comparison of 24-h IC-C/IC-I ratios in the obese and nonobese subjects. Whereas the 24-h IC-C/IC-I of the nonobese resembled the fasting state, the 24-h IC-C/IC-I of the obese resembled the postprandial state, when insulin removal by the liver is known to be suppressed. These data are consistent with a decreased 24-h hepatic MCR-I (hMCR-I) as the cause of the hyperinsulinemia of obesity.

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