ELIMINATION OF INFUSED ARGININE-VASOPRESSIN AND ITS LONG-ACTING DEAMINATED ANALOGUE IN RATS

1978 ◽  
Vol 78 (2) ◽  
pp. 179-186 ◽  
Author(s):  
DIANA GAZIS ◽  
W. H. SAWYER

SUMMARY Arginine-vasopressin (AVP) and deamino-arginine-vasopressin (dAVP) were infused into rats. When the concentrations of the two peptides were steady, the rate of clearance of AVP from the plasma was six times the rate of clearance of dAVP. Only 6% of the infused AVP was excreted unchanged in the urine, whereas approximately 100% of the dAVP was excreted. When the infusions were stopped, AVP disappeared from the plasma much more rapidly than dAVP. The plasma concentrations of the two peptides did not decay as simple exponential functions, suggesting that both AVP and dAVP entered a slowly exchanging compartment or compartments during prolonged infusion. These differences in the metabolic clearance of AVP and dAVP may well explain the prolonged antidiuretic effect of dAVP in rats.

1986 ◽  
Vol 70 (5) ◽  
pp. 409-416 ◽  
Author(s):  
J. J. Dixey ◽  
T. D. M. Williams ◽  
S. L. Lightman ◽  
A. F. Lant ◽  
D. A. Brewerton

1. The renal response to graded intravenous infusions of arginine vasopressin (AVP) was investigated in a two part study in six volunteers. First, under maximal water diuresis, seven control incremental infusions of AVP were given from zero to 12 fmol min−1 kg−1. Second, the AVP infusions were repeated after pretreatment with indomethacin, 150 mg daily for 36 h. 2. After the AVP infusions, plasma AVP concentrations did not change significantly and remained within the physiological range; in contrast, urinary AVP excretion rate increased steadily. Indomethacin did not alter the plasma or urinary concentrations of AVP. 3. AVP caused a fall in urine flow rate from a state of maximal diuresis to one of maximal anti-diuresis. After indomethacin, fractional free water clearance was reduced by an average of 26% at the zero, 2 and 4 fmol min−1 kg−1 infusion rates of AVP. 4. A significant increase in fractional sodium clearance of approximately 50% occurred during the AVP infusions, which was abolished after pretreatment with indomethacin. 5. After indomethacin, urinary prostaglandin E2 (PGE2) excretion rate was reduced by an average of 40%) at the zero and 2 fmol min−1 kg−1 infusion rates of AVP. At higher AVP infusion rates, no significant inhibition of PGE2 was observed. 6. Urinary kallikrein excretion rate decreased steadily to one-third of its original value after AVP and this change remained unaltered by indomethacin. 7. The findings show that infusions of AVP, resulting in plasma concentrations in the physiological range, evoke a maximal antidiuretic response, which is accompanied by natriuresis. Significant inhibition of urinary prostaglandin excretion by indomethacin is accompanied by both enhancement of the antidiuretic effect of an abolition of the natriuretic response to AVP.


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.


1985 ◽  
Vol 108 (2) ◽  
pp. 179-183 ◽  
Author(s):  
Stefan Lundin ◽  
Per Melin ◽  
Hans Vilhardt

Abstract. A sensitive and specific radioimmunoassay for 1-deamino-8-d-arginine vasopressin (DDAVP) was developed. Plasma concentrations of DDAVP after intragastric administration were determined in non-fasted rats and a dose-related increase in plasma levels was obtained. The immunoidentity of plasma DDAVP and standard was established by high performance liquid chromatography (HPLC). Correlation of biological and immunological responses of DDAVP was assessed using the antidiuretic effect in the Brattleboro (diabetes insipidus) rat.


2006 ◽  
Vol 191 (2) ◽  
pp. 491-496 ◽  
Author(s):  
Getu Abraham ◽  
Fioralba Demiraj ◽  
Fritz Rupert Ungemach

The effects of single injections of glucocorticoid (GC) depot suspension and of long-acting GC were studied in conscious dogs. Both the depot suspension GC triamcinolone-16,17-α-acetonide (TAA) and the long-acting triamcinolone acetonide-21-dihydrogen phosphate (TAA-DHP) decreased basal and ACTH-stimulated cortisol levels and in a specific time-dependent way. Before treatment, all dogs had normal basal and peak cortisol responses to ACTH challenge (13–15 and > 120 nmol/l at 1 h respectively). Intravenous TAA-DHP reduced cortisol levels for 12 h, i.m. TAA reduced cortisol levels as of 1.5 h and the effect lasted for at least 4 weeks. Both treatments blunted the peak response to ACTH. ACTH elevated cortisol levels to or above baseline values within 10 days following TAA-DHP treatment, but the TAA treatment suppressed an ACTH response for at least 4 weeks. Kinetic analysis of both the preparations demonstrated rapid absorption (tmax, 0.6–1.5 h) and low maximum plasma concentrations (peak Cmax, 2.99–5.51 nmol/l) of the steroids; indeed, the terminal half-life of TAA-DHP (13.9 ± 1.3 h) was very much shorter than that of TAA (125.9 ± 15.8 h). In addition, the mean residence time differed very much (11 vs 160 h for TAA-DHP and TAA respectively), in line with a delayed elimination of the depot compared with the long-acting formulation. Application of these TAA formulations needs careful evaluation for their surprisingly different effects on endocrine stress axis activity.


1995 ◽  
Vol 88 (2) ◽  
pp. 197-201 ◽  
Author(s):  
S. L. Carney ◽  
A. H. B. Gillies

1. It has been demonstrated that parathyroid hormone can increase adenylate cyclase activity in the rat papilla, produce a small antidiuretic effect and in vitro can interfere with the action of arginine vasopressin on water transport. Clearance studies were performed in the anaesthetized water diuretic thyroparathyroidectomized rat to evaluate further the effect of parathyroid hormone on urine concentration in the presence and absence of arginine vasopressin. 2. A maximal phosphaturic concentration of rat parathyroid hormone (2 μg/kg) reduced urine flow from 125 ± 7 to 81 ± 9 μl/min within 10 min (P < 0.01). Addition of a maximal antidiuretic concentration of arginine vasopressin (100 ng/kg) produced a delayed and diminished antidiuretic response when compared with a group of rats not pretreated with parathyroid hormone (47 ± 5 compared with 27 ± 5 μl/min; P < 0.01). However, a supramaximal arginine vasopressin concentration (1000 ng/kg) produced a maximal antidiuretic effect in the presence of parathyroid hormone. 3. To evaluate further the inhibitory effect of parathyroid hormone on arginine vasopressin-induced anti-diuresis, parathyroid hormone (2 μg/kg) was administered to one group of rats and a minimally effective arginine vasopressin concentration (7.5 ng/kg) to another group, which produced a similar antidiuretic effect. However, the subsequent effect of a maximal antidiuretic arginine vasopressin concentration (100 ng/kg) was again significantly blunted in the group pretreated with parathyroid hormone. 4. Parathyroid hormone produced only a small increase in mean plasma calcium concentration, and glomerular filtration rate was not altered by either hormone. 5. These results demonstrate that high physiological concentrations of parathyroid hormone do have a significant antidiuretic effect and can interfere with the action of arginine vasopressin. This suggests that parathyroid hormone may act as a partial agonist to arginine vasopressin in the collecting system.


1993 ◽  
Vol 49 (1) ◽  
pp. 1-7 ◽  
Author(s):  
Klaus Hermann ◽  
Cordula Ebner von Eschenbach ◽  
Marietta von Tschirschnitz ◽  
Johannes Ring

1985 ◽  
Vol 249 (1) ◽  
pp. E49-E55 ◽  
Author(s):  
R. P. Naden ◽  
S. Coultrup ◽  
B. S. Arant ◽  
C. R. Rosenfeld

Reduced vascular responsiveness to infused angiotensin II (ANG II) has been observed during pregnancy. It has been proposed that infusions produce lower circulating concentrations of ANG II in pregnancy, due to an increase in the metabolic clearance rate of ANG II (MCRangii). We have evaluated the MCRangii and the arterial plasma concentrations of ANG II during constant infusions of 1.15 micrograms ANG II/min into chronically instrumented pregnant (n = 6) and nonpregnant (n = 9) sheep. Although the pressor responses were significantly less in the pregnant than in the nonpregnant sheep (17.5 +/- 0.5 vs. 34.9 +/- 3.2 mmHg, P less than 0.001), the values for MCRangii were not different: 56.2 +/- 6.3 ml X min-1 X kg-1 in nonpregnant and 55.9 +/- 4.3 ml X min-1 X kg-1 in pregnant sheep. The steady-state plasma ANG II concentrations during the infusions were slightly less in pregnant than in nonpregnant sheep (388 +/- 36 vs. 454 +/- 36 pg/ml); however, this difference would be responsible for only a 2-mmHg reduction in the pressor response. We conclude that the reduced pressor response to infused ANG II in pregnancy is not due to an increase in MCRangii nor to lower plasma ANG II concentrations.


1986 ◽  
Vol 66 (4) ◽  
pp. 995-1001
Author(s):  
G. J. MEARS

Plasma concentrations of growth hormone (GH) and insulin were monitored in 11 chronically cannulated ovine fetuses and their mothers during the last month of gestation to obtain information on the role that these hormones have in determining fetal growth rate. Maternal plasma GH and insulin concentrations were independent of stage of gestation and lamb birth weights. Fetal plasma insulin concentrations were episodic in nature, independent of stage of gestation, and tended to be higher in fetuses that were heavier at birth. Fetal plasma GH concentrations were only slightly episodic in nature, were tenfold higher than maternal levels at 116–124 d gestation and increased by approximately another 25% prior to parturition. Fetal plasma GH concentrations were negtively correlated with lamb birth weights. In twin preparations, fetal plasma GH concentrations were significantly lower in the twin that was heaviest at birth. The lower GH concentrations found in faster growing fetuses are suggestive of a more rapid metabolic clearance of GH by the tissues of these animals. The results indicate that circulating fetal GH and, possibly, insulin are involved in determining the rate of ovine-fetal growth. Key words: Ovine birth weights, fetal GH, fetal insulin, fetal growth


2019 ◽  
Vol 58 (7) ◽  
pp. 716-724 ◽  
Author(s):  
Douglas L Feinstein ◽  
Daniel G Nosal ◽  
Swetha Ramanathan ◽  
Jifang Zhou ◽  
Luying Chen ◽  
...  

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