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

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.

1980 ◽  
Vol 93 (3) ◽  
pp. 277-282 ◽  
Author(s):  
Derek LeRoith ◽  
Gabriel Danovitz ◽  
Stefan Trestian ◽  
Irving M. Spitz

Abstract. The LH, FSH and TSH response to LRH and TRH has been evaluated in patients with chronic renal failure. Basal gonadotrophins were elevated in 3 out of 6 males; one of 4 pre-menopausal females had increased basal LH. Exaggerated LH responses to LRH were noted in 4 out of 6 males and one of 4 females; FSH responses were increased in 3 of these males. One male and one female had attenuated LH and FSH responses to LRH. Both testosterone and oestradiol levels were reduced. In 5 out of 6 subjects tested both pre- and post-dialysis there was a greater LH and FSH response to LRH following dialysis. This suggests the presence of a dialysable toxin which is inhibiting the gonadotrophin response to LRH. Gonadotrophin levels remained elevated during 4 h of dialysis suggesting prolongation of the metabolic clearance rate. Despite low T3 levels, TSH response to TRH (200 μg) was only elicited in 2 of 6 cases. However, all 3 responded to 500 μg and 2 out of 3 to 1000 μg TRH, the third showing an attenuated response. TSH levels also remained persistently elevated in the responders. Dialysis however, failed to improve the relative TSH non-responsiveness to TRH. In conclusion the data has shown that there is a dissociation in glycoprotein hormone responses to releasing hormones in uraemia. Whereas the gonadotrophs retain their responsiveness to LRH, the thyrotrophs appear to be more effected by the uraemic process and demonstrate an impaired response to TRH.


1978 ◽  
Vol 44 (1) ◽  
pp. 5-11 ◽  
Author(s):  
E. O. Balasse ◽  
F. Fery ◽  
M. A. Neef

Seven normal subjects fasted for 3 days were exercised for 30 min on a bicycle ergometer at 60 +/- 30% (mean +/- SE) of their maximal aerobic capacity. Rates of transport and oxidation of ketone bodies were determined at rest and during exercise using a primed constant infusion of [14C]acetoacetate. During the initial 7.5 min of exercise, ketone concentration abruptly decreased (-19.4 +/- 3.1%; P less than 0.001) as the result of a 22.2 +/- 7.0% reduction (P less than 0.05) in ketone production rate (Ra) and a 30.4 +/- 7.5% increase (P less than 0.01) in the rate of uptake (Rd) of ketones. As work progressed, blood ketones continued to fall slowly until the 15th min of exercise and thereafter plateaued at a level which was 21.9 +/- 4.1% lower (P less than 0.005) than resting values. During this apparent new steady state, both Ra and Rd were below control values but tended to be equal and to return simultaneously to their preexercise level. The metabolic clearance rate was increased throughout the entire period of exercise, the rise being more marked during the initial 7.5 min (+40.7 +/- 7.5%; P less than 0.01) than at later periods (+19.0 +/- 7.4%; P less than 0.05). Exercise greatly enhanced ketone oxidation which became virtually complete; despite this, the %CO2 derived from ketones, which averaged 17.6 +/- 1.6% at rest, decreased to 10.1 +/- 0.6% (P less than 0.01) after 30 min of work. This indicates that even during the hyperketonemia of fasting, the increased energy needs related to exercise are met primarily by fuels other than ketones.


1987 ◽  
Vol 252 (3) ◽  
pp. E431-E438 ◽  
Author(s):  
J. M. Miles ◽  
M. G. Ellman ◽  
K. L. McClean ◽  
M. D. Jensen

The accuracy of tracer methods for estimating free fatty acid (FFA) rate of appearance (Ra), either under steady-state conditions or under non-steady-state conditions, has not been previously investigated. In the present study, endogenous lipolysis (traced with 14C palmitate) was suppressed in six mongrel dogs with a high-carbohydrate meal 10 h before the experiment, together with infusions of glucose, propranolol, and nicotinic acid during the experimental period. Both steady-state and non-steady-state equations were used to determine oleate Ra ([3H]oleate) before, during, and after a stepwise infusion of an oleic acid emulsion. Palmitate Ra did not change during the experiment. Steady-state equations gave the best estimates of oleate inflow approximately 93% of the known oleate infusion rate overall, while errors in tracer estimates of inflow were obtained when non-steady-state equations were used. The metabolic clearance rate of oleate was inversely related to plasma concentration (P less than 0.01). In conclusion, accurate estimates of FFA inflow were obtained when steady-state equations were used, even under conditions of abrupt and recent changes in Ra. Non-steady-state equations, in contrast, may provide erroneous estimates of inflow. The decrease in metabolic clearance rate during exogenous infusion of oleate suggests that FFA transport may follow second-order kinetics.


1986 ◽  
Vol 251 (2) ◽  
pp. R365-R370 ◽  
Author(s):  
A. M. Moses ◽  
E. Steciak

Synthetic arginine vasopressin (AVP) was infused into 11 hydrated normal subjects at five different infusion rates ranging from 10 to 350 microU X kg-1 X min-1. Each infusion rate was continued for 1 h, and urinary determinations were made on the 30- to 60-min specimens during which time there was no further rise in plasma AVP. Urinary AVP concentrations (microU/ml) and excretion rates (microU/min) increased linearly with increasing infusion rates, and the concentration of AVP in urine increased 120 times more rapid than plasma. Urinary and metabolic clearances of AVP also increased linearly with the maximum urinary clearance being 60.6% of the creatinine clearance. The total metabolic clearance of AVP (including urinary clearance) was 17.8 times that of the urinary clearance of AVP alone. These data clarify the relationships between plasma and urinary AVP in normal hydrated subjects during AVP infusion under steady-state conditions and emphasize the potential advantage of measuring urinary AVP as a monitor of endogenous AVP secretion.


2020 ◽  
Vol 52 (7S) ◽  
pp. 597-597
Author(s):  
Lee M. Margolis ◽  
Marques A. Wilson ◽  
Claire C. Whitney ◽  
Christopher T. Carrigan ◽  
Nancy E. Murphy ◽  
...  

1982 ◽  
Vol 242 (2) ◽  
pp. G177-G182
Author(s):  
M. C. Geokas ◽  
R. Reidelberger ◽  
M. O'Rourke ◽  
E. Passaro ◽  
C. Largman

The kidney has previously been shown to be a major site for the plasma clearance of pancreatic trypsinogens in the rat. This study investigated plasma concentrations of anionic and cationic trypsinogen in chronic renal failure and anephric patients. Plasma concentrations were significantly elevated in both groups of patients. Hemodialysis did not change their plasma levels. The plasma levels of anionic and cationic trypsinogens were highly correlated in patients and normal subjects; however, the relative concentrations of anionic trypsinogen were significantly higher in renal failure patients. This suggests that in patients with renal failure the secondary clearance mechanisms for these plasma proteins more efficiently clear cationic molecules. In normal dogs, intravenous infusion of synthetic octapeptide of cholecystokinin (CCK-8) resulted in small transitory increases in plasma trypsinogen levels. After nephrectomy, basal levels of anionic and cationic trypsinogen were elevated, and intravenous infusion of CCK-8 resulted in prolonged, high levels of plasma trypsinogens.


1986 ◽  
Vol 250 (5) ◽  
pp. E495-E501 ◽  
Author(s):  
F. Fery ◽  
E. O. Balasse

This study examines the effects of a 2-h exercise of moderate intensity (50% of VO2 max) on the tracer-determined turnover rate of ketone bodies (KB) in 21 normal subjects fasted for 16 h, 5 days, whose basal ketonemia ranged between 0.09 and 6.16 mM. The KB response observed at the end of exercise is a function of the initial degree of ketosis. When basal ketonemia is below 0.6 mM, exercise enhances ketogenesis (Ra), the amplitude of this process being positively correlated with KB level. There is a concomitant acceleration of the metabolic clearance rate (MCR) of KB attaining 40-50%. When ketonemia exceeds 2.5 mM, the stimulatory effects of exercise on Ra and on MCR become less marked as basal ketonemia rises and are completely abolished or even reversed when initial KB level is higher than 3-4 mM. The pattern of changes in the concentration and in the overall disposal rate of KB were similar to that of Ra. It is suggested that the parallel inhibition of the stimulatory effect of work on hepatic ketogenesis and on muscular extraction of ketones associated with increasing degrees of fasting hyperketonemia has two physiological implications: it maintains the preferential utilization of KB by nonmuscular tissues (presumably the brain) and prevents the development of uncontrolled hyperketonemia, despite the intense catabolic situation created by the combination of exercise and starvation.


1978 ◽  
Vol 55 (s4) ◽  
pp. 89s-92s ◽  
Author(s):  
S. Ghione ◽  
C. Palombo ◽  
M. Pellegrini ◽  
E. Fommei ◽  
A. Pilo ◽  
...  

1. The kinetics of plasma noradrenaline have been determined in normal and essential hypertensive patients by intravenous injection of tritiated noradrenaline and serial mixed venous sampling. 2. The metabolic clearance rate of plasma noradrenaline in normal subjects was approximately 1·1 min−1 m−2, whereas in essential hypertensive patients it was significantly reduced to approximately 0·61 min−1 m−2. 3. Metabolic clearance rate was negatively correlated to mean arterial blood pressure and total peripheral resistances. 4. Particularly low values of metabolic clearance rate were found in two patients with congestive heart failure and one with phaeochromocytoma. 5. We propose that the access of plasma noradrenaline to the main removal mechanisms takes place in competition with the flow of unlabelled endogenous noradrenaline directly released by nerve endings. The slower removal of plasma noradrenaline in essential hypertension could then express a larger release of endogenous noradrenaline in this condition.


1988 ◽  
Vol 118 (1) ◽  
pp. 25-31 ◽  
Author(s):  
K. G. Braslis ◽  
A. Shulkes ◽  
D. R. Fletcher ◽  
K. J. Hardy

ABSTRACT Calcitonin gene-related peptide (CGRP) is a product of the calcitonin gene with a widespread distribution in neural tissue of the brain, gut and perivascular nerves. Infusion of CGRP produces multiple biological effects, but the physiological significance of these findings will be influenced by the sites and rates of CGRP metabolism. The metabolic clearance rate and half-life of disappearance of human CGRP were estimated in conscious sheep after infusing CGRP at 1 or 5 pmol/kg per min to steady-state conditions. The particular organs involved in the clearance of CGRP were assessed by measuring the inflow and outflow concentrations across the liver, gut, kidney, lung and brain. The metabolic clearance rate at steady state was 22·6 ± 2·1 (s.e.m.) and 15·0±1·7 ml/kg per min for the 1 and 5 pmol/kg per min doses respectively. The half-life of disappearance was bi-exponential: 3·6±0·3 min for the first phase and 13·6±1·0 min for the second phase. High-pressure liquid chromatography of plasma at equilibrium revealed only a single peak coeluting with CGRP(1–37): no immunoreactive metabolites were detected. These pharmacokinetic values are intermediate between that of a neurotransmitter and a hormone and are therefore consistent for a peptide with both circulatory and neurotransmitter modes of action. The kidney, with an arterial–renal vein gradient of 14%, and the liver, with a portal– hepatic vein gradient of 25%, were the major organs involved in the clearance of CGRP. The specific organ clearance, however, accounted for only one-third of the whole body metabolic clearance rate of CGRP, suggesting that other more generalized degradative systems are involved, such as endothelial-bound enzymes of blood vessels. This information on clearance and organ-specific metabolism should form a basis for evaluating the physiological roles and modes of action of CGRP. J. Endocr. (1988) 118,25–31


Sign in / Sign up

Export Citation Format

Share Document