Effects of Endopeptidase 24.11 Inhibition on Plasma and Tissue Concentrations of Vasoactive Intestinal Peptide

1995 ◽  
Vol 89 (3) ◽  
pp. 267-271 ◽  
Author(s):  
K. A. Duggan ◽  
D. M. Jones ◽  
V. Z. C. Ye ◽  
R. E. Davis ◽  
G. J. MacDonald
Keyword(s):  
Angiotensin Ii ◽  
Vasoactive Intestinal Peptide ◽  
Clearance Rate ◽  
Chronic Administration ◽  
Metabolic Clearance ◽  
Sprague Dawley ◽  
Metabolic Clearance Rate ◽  
Tissue Concentrations ◽  
Endopeptidase 24.11 ◽  
Sprague Dawley Rats

1. In this study, we sought to determine the effect of endopeptidase 24.11 inhibition on the rate of metabolism of vasoactive intestinal peptide. The effect of such inhibition on the concentration of vasoactive intestinal peptide in two tissues was also investigated. 2. Male Sprague—Dawley rats were given the endopeptidase 24.11 blocker UK77,568 (10 mg/kg) or vehicle as a single intravenous injection or as a daily injection for 4 days. Two hours after the final or single injection, the rats were anaesthetized and blood was sampled to determine plasma concentrations of vasoactive intestinal peptide and angiotensin II. The hearts and kidneys were harvested and snap-frozen in liquid nitrogen. The plasma and tissue concentrations of vasoactive intestinal peptide and the plasma concentration of angiotensin II were determined by radioimmunoassay. In a separate group of experiments, male Sprague—Dawley rats were anaesthetized and carotid and jugular catheters were inserted. One hour after intravenous administration of UK77,568 or vehicle, an infusion of vasoactive intestinal peptide (10 pmol min−1 kg−1) was commenced via the jugular catheter. Blood was sampled to determine the vasoactive intestinal peptide concentration 1 h after commencing the vasoactive intestinal peptide infusion to calculate the metabolic clearance rate. 3. Plasma vasoactive intestinal peptide increased after acute (P < 0.05) but not chronic administration of UK77,568, while the concentration of vasoactive intestinal peptide in the heart increased after chronic administration (P < 0.0005). The concentration of vasoactive intestinal peptide in the kidney was unchanged after both acute and chronic endopeptidase 24.11 blockade. Plasma angiotensin II decreased significantly in the chronic group (P < 0.05). The metabolic clearance rate of vasoactive intestinal peptide decreased significantly after UK77,568 administration (P < 0.05). 4. These studies add to the existing indirect evidence that endopeptidase 24.11 may metabolize vasoactive intestinal peptide in addition to a number of other hormones.

Angiotensin II regulates the metabolism but not the secretion of vasoactive intestinal peptide in the rabbit

1992 ◽  
Vol 83 (5) ◽  
pp. 557-560 ◽  
Author(s):  
R. E. Davis ◽  
G. J. MacDonald ◽  
K. A. Duggan
Keyword(s):  
Angiotensin Ii ◽  
Vasoactive Intestinal Peptide ◽  
Clearance Rate ◽  
Sodium Intake ◽  
Secretion Rate ◽  
Dietary Sodium ◽  
Metabolic Clearance ◽  
Metabolic Clearance Rate ◽  
High Sodium ◽  
Significant Difference

1. We have previously demonstrated that the metabolism and secretion of vasoactive intestinal peptide are affected by both acute and chronic dietary sodium. Sodium concentrations in portal and systemic plasma were unaffected by differing levels of sodium intake or administration of an acute gastric sodium load. We sought, therefore, to determine whether other hormones involved in sodium homoeostasis (such as angiotensin II) might be involved in regulating the metabolism and secretion of vasoactive intestinal peptide. We determined the metabolic clearance rate and theoretical secretion rate of vasoactive intestinal peptide in rabbits on low sodium (high circulating angiotensin II) and high sodium (low circulating angiotensin II) diets with and without simultaneous angiotensin II infusion. 2. The metabolic clearance rate of vasoactive intestinal peptide was significantly higher in rabbits on the high sodium diet during both vehicle control (P<0.01) and angiotensin II (P<0.05) infusion. Angiotensin II infusion decreased the metabolism of vasoactive intestinal peptide in rabbits on both low (P<0.01) and high (P<0.01) sodium diets. 3. Although there was a significant difference in secretion rates between the two dietary groups (P<0.025) under basal conditions, infusion of angiotensin II did not alter the secretion rate significantly in either group. 4. We conclude that angiotensin II regulates the metabolism of vasoactive intestinal peptide in the rabbit, but does not regulate its secretion.

Angiotensin II metabolic clearance rate and pressor responses in nonpregnant and pregnant women

1994 ◽  
Vol 171 (3) ◽  
pp. 668-679 ◽  
Author(s):  
Ronald R. Magness ◽  
Kay Cox ◽  
Charles R. Rosenfeld ◽  
Norman F. Gant
Keyword(s):  
Angiotensin Ii ◽  
Pregnant Women ◽  
Clearance Rate ◽  
Metabolic Clearance ◽  
Metabolic Clearance Rate ◽  
Pressor Responses

Metabolic clearance rate of radioiodinated angiotensin II in normal men

1972 ◽  
Vol 223 (5) ◽  
pp. 1250-1256 ◽  
Author(s):  
L Donato ◽  
A Coli ◽  
R Pasqualini ◽  
T Duce
Keyword(s):  
Angiotensin Ii ◽  
Clearance Rate ◽  
Metabolic Clearance ◽  
Metabolic Clearance Rate ◽  
Normal Men

ANF disappearance and tissue distribution in rats

1990 ◽  
Vol 258 (1) ◽  
pp. H134-H139
Author(s):  
J. Widimsky ◽  
W. Debinski ◽  
O. Kuchel ◽  
N. T. Buu
Keyword(s):  
Tissue Distribution ◽  
Atrial Natriuretic Factor ◽  
Volume Of Distribution ◽  
Metabolic Clearance ◽  
Sprague Dawley ◽  
Metabolic Clearance Rate ◽  
Sprague Dawley Rats ◽  
The Brain ◽  
Lung And Kidney ◽  
Radioactivity Levels

The disappearance of [125I]atrial natriuretic factor (ANF; Ser99-Tyr126) from the circulation and its tissue distribution with or without nonlabeled ANF pretreatment were investigated in normotensive Sprague-Dawley rats. Preadministration of the cold peptide increased plasma radioactivity levels for over 8 min following labeled ANF injection but did not change the half-life of circulating labeled ANF. The metabolic clearance rate (MCR) and volume of distribution in the first, second, and steady state phase were significantly decreased after cold ANF pretreatment. Circulating iodo-labeled ANF was taken up by several organs, even by tissues such as fat or bone, but its urinary excretion was very low. The highest uptake was found in the liver (16 +/- 1% of the injected dose), lung (14 +/- 1%), and kidney (12 +/- 1%), diminishing by 21, 89, and 59%, respectively, after cold ANF preinjection. The brain radioactivity was negligible implying an inability of [125I]ANF to cross the blood-brain barrier. Our data underscore the importance of the uptake-mediated, cold ANF preadministration suppressible clearance of ANF from the circulation, probably one of its basic elimination mechanisms. The liver, lung, and kidney are probably the most important participants in the MCR of ANF.

Metabolic Clearance Rate of Angiotensin II in Arterial Hypertension

1973 ◽  
Vol 45 (s1) ◽  
pp. 235s-238s
Author(s):  
A. Coli ◽  
L. Donato
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Arterial Hypertension ◽  
Clearance Rate ◽  
Control Mechanism ◽  
Blood Pressure Level ◽  
Pressure Level ◽  
Metabolic Clearance ◽  
Metabolic Clearance Rate ◽  
Additional Control

1. Plasma metabolic clearance rate of mono-[125I]iodoangiotensin II was measured in seventeen patients with various disorders of the renin-angiotensin-aldosterone system. The measurements were carried out by using a new method which accounts for the contribution of labelled split products. 2. A significant correlation was obtained (P < 0.01), when plasma metabolic clearance rate was related to mean blood pressure level and the correlation appeared independent of angiotensin II presumed concentration. 3. A possible additional control mechanism of angiotensin II degradation is suggested. RIASSUNTO 1. Gli autori hanno misurato la clearance metabolica della mono-[125I]iodoangiotensina II in 17 pazienti con varie alterazioni del sistema renina-angiotensina-aldosterone. Il metodo impiegato permette la sottrazione diretta della radioattività plasmatica dovuta all'angiotensina, da quella dei frammenti marcati. 2. Si osserva una correlazione significativa (P < 0.01), quando i valori di clearance sono confrontati con quelli della pressione arteriosa media. 3. Viene supposto un ulteriore possibile sistema di controllo nella degradazione della angiotensina II.

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

scholarly journals The Renin-Angiotensin System in Conscious Newborn Sheep: Metabolic Clearance Rate and Activity

2007 ◽  
Vol 61 (6) ◽  
pp. 681-686 ◽  
Author(s):  
Sithembiso C Velaphi ◽  
Kevin Despain ◽  
Timothy Roy ◽  
Charles R Rosenfeld
Keyword(s):  
Clearance Rate ◽  
Renin Angiotensin System ◽  
Metabolic Clearance ◽  
Metabolic Clearance Rate ◽  
Angiotensin System ◽  
Renin Angiotensin

Validation of a new method for determination of free fatty acid turnover

1987 ◽  
Vol 252 (3) ◽  
pp. E431-E438 ◽  
Author(s):  
J. M. Miles ◽  
M. G. Ellman ◽  
K. L. McClean ◽  
M. D. Jensen
Keyword(s):  
Steady State ◽  
Fatty Acid ◽  
Free Fatty Acid ◽  
Clearance Rate ◽  
Experimental Period ◽  
Metabolic Clearance ◽  
Metabolic Clearance Rate ◽  
State Equations ◽  
Tracer Methods

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.

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