The effect of indomethacin on the renal response to arginine vasopressin in man

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.

1975 ◽  
Vol 80 (3) ◽  
pp. 453-464 ◽  
Author(s):  
U. Merkelbach ◽  
P. Czernichow ◽  
R. C. Gaillard ◽  
M. B. Vallotton

ABSTRACT A radioimmunoassay for [8-arginine]-vasopressin (AVP), previously described (Czernichow et al. 1975) has been used for the determination of antidiuretic hormone in a 4 ml urine sample. AVP is extracted from acidified urine with a cation exchanger (Amberlite CG 50) with an overall recovery of 72 %. The blank value measured in extracted samples of urine was 0.29 pg/ml ± 0.21 (sem) and calculated by extrapolation of the regression line of the recovery experiment was 0.49 pg/ml. The coefficient of variation within-assay was 13 % and between-assay 18%. Addition of the amounts of AVP found in each specimen of urine voided gave results nearly identical to those of the amounts found in 24 h pool of urine, indicating that the assay was not affected by changes in concentration of the other urinary components during the day. The daily urinary excretion of AVP measured in 34 subjects was found to be 34 ng in 17 women and 70 ng in 17 men, a significant difference. Urinary concentration and excretion rate of AVP rose during thirst test and during Carter-Robbins test performed in 13 healthy subjects. In the latter test it was observed that the women displayed a strikingly more pronounced AVP elevation after the osmolar stimulus than the men. In both sexes a significant correlation was found between AVP excretion rate and plasma osmolality as well as free water clearance. Three cases of complete or incomplete diabetes insipidus and potomania could be clearly differentiated according to the total output of AVP during the thirst test. Extremely high values of AVP were found in the urine of 5 subjects with Schwartz-Bartter syndrome associated with bronchogenic tumours.


1988 ◽  
Vol 74 (6) ◽  
pp. 571-576 ◽  
Author(s):  
K. P. Walsh ◽  
T. D. M. Williams ◽  
R. Canepa-Anson ◽  
P. Roe ◽  
E. Pitts ◽  
...  

1. The relationships between the haemodynamic, renal and endocrine changes induced by rapid ventricular pacing were studied in ten chloralose-anaesthetized dogs paced from the right ventricular apex for 60 min at 250 beats/min. 2. Pacing increased mean right atrial and mean pulmonary wedge pressure (P < 0.05), and decreased cardiac output and mean arterial pressure (P < 0.05). 3. Coronary sinus atrial natriuretic peptide (ANP) concentrations were approximately fourfold greater than arterial concentrations; both increased markedly during pacing (P < 0.01). Plasma concentrations of arginine vasopressin and plasma renin activity did not change signficantly. 4. Urine flow and free water clearance increased during the latter 30 min of pacing (P < 0.05). There was no significant change in sodium clearance despite high sustained concentrations of ANP. 5. Without the availability of specific inhibitors of ANP release or action, we are unable to exclude the possibility that ANP may have prevented sodium clearance from otherwise decreasing during rapid ventricular pacing. Nevertheless, the dissociation between elevated ANP concentrations and natriuresis in this study indicates that a rise in ANP concentrations per se is not sufficient to produce a natriuresis.


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.


1979 ◽  
Vol 237 (5) ◽  
pp. E428
Author(s):  
N Brautbar ◽  
B S Levine ◽  
J W Coburn ◽  
C R Kleeman

Six conscious intact dogs were studied to evaluate the interactions of somatostatin (SRIF) with exogenous antidiuretic hormone arginine vasopressin (AVP). SRIF administration caused a significant increase in free water clearance compared to a vehicle-treated group: -0.91 (+/- 0.41 SD) ml/min to 0.21 (+/- 0.32 SD) ml/min in the experimental group (P less than 0.01) versus 0.21 (+/- 0.81 SD) ml/min to -0.21 (+/- 0.68 SD) ml/min in the control (P greater than 0.5). Six conscious, thyroparathyroidectomized dogs were studied to test the interaction of SRIF and parathyroid extract (PTE). There were no significant changes in the phosphaturic and hypocalciuric effects of PTE with SRIF administration. We conclude that acute systemic SRIF administration interferes with the antidiuretic action of AVP, probably at the renal-tubular level, but does not antagonize the renal actions of PTE.


1998 ◽  
Vol 275 (4) ◽  
pp. R1058-R1065 ◽  
Author(s):  
Charles E. Wade ◽  
Emily Morey-Holton

Following spaceflight, changes in renal function of humans have been suggested. To assess the effects of readaptation on renal function, urine was collected from male rats (∼245 g) over a 2-wk period following a 14-day spaceflight. Rats were assigned to three groups: flight animals ( n = 6), flight controls ( n = 6) housed in the flight cages on the ground, and vivarium controls ( n = 5) housed in standard shoe box cages. Animals were placed into individual metabolic cages for urine collection. Urine output was significantly increased for 3 days following flight. Excretion rates of Na+ and K+ were increased, resulting in an increased osmotic excretion rate. Creatinine excretion rate increased over the first two postflight days. Glomerular filtration rate increased immediately following spaceflight without changes in plasma creatinine, Na+, K+, or osmolality. Increased excretion of solute was thus the result of increased delivery and a decreased percent reabsorption of the filtered load. Osmolal clearance was increased immediately postflight while free water clearance was decreased. In growing rats, the diuresis after short-duration spaceflight is the result of an increase in solute excretion with an accompanying reduction in free water clearance.


1993 ◽  
Vol 264 (1) ◽  
pp. E37-E44 ◽  
Author(s):  
R. J. MacIsaac ◽  
R. S. Horne ◽  
I. W. Caple ◽  
T. J. Martin ◽  
E. M. Wintour

The fetal parathyroid glands and parathyroid hormone-related protein (PTHrP) have been shown to be important regulators of fetal calcium metabolism through their actions on the placenta and bone. This study examined the effects of fetal thyroparathyroidectomy (with thyroxine replacement) and exogenous infusion of human parathyroid hormone [PTH-(1–34)], PTHrP-(1–34), and PTHrP-(1–141) on the urinary excretion of calcium in chronically cannulated ovine fetuses during the last one-fifth of gestation. Fetal plasma total and ionized calcium concentrations were significantly lower in thyroparathyroidectomized (TxPTx) fetuses when compared with intact fetuses, but there were no significant differences in urinary excretion rates of total calcium. However, TxPTx produced a significant increase in the fractional excretion rate of total calcium and a significant decrease in the excretion of adenosine 3',5'-cyclic monophosphate (cAMP) compared with intact fetuses. Infusions of PTH-(1–34), PTHrP-(1–34), and PTHrP-(1–141) into the jugular vein of TxPTx fetuses (n = 5) at the rate of 1 nmol/h for 2 h, after a 1-nmol loading dose, significantly decreased the excretion rate of total calcium and increased the excretion rate of cAMP in fetal urine. Infusions of all three peptides resulted in significant increases in the concentration of total calcium in fetal plasma but had no effect on the plasma concentrations or urinary excretion rates of phosphate. Infusion of either PTH-(1–34), PTHrP-(1–34), or PTHrP-(1–141) also resulted in an increase in fetal urine osmolality and pH and a decrease in free water clearance in TxPTx fetuses.(ABSTRACT TRUNCATED AT 250 WORDS)


1986 ◽  
Vol 71 (1) ◽  
pp. 97-104 ◽  
Author(s):  
E. B. Pedersen ◽  
H. Danielsen ◽  
S. S. Sørensen ◽  
B. Jespersen

1. An oral water load of 20 ml/kg body wt. was given to eight patients with nephrotic syndrome before and after remission of the syndrome, and to 13 healthy control subjects. Urine volume (D), free water clearance (Cwater), plasma concentrations of arginine vasopressin (AVP), angiotensin II (ANG II) and aldosterone (Aldo), were determined before and three times during the first 4 h after loading. 2. D and Cwater increased to a significantly lower level (P < 0.01) after water loading in patients with nephrotic syndrome than in control subjects, but D and Cwater were normal after remission of the syndrome. The maximum increase in Cwater (ΔCwater max.) was 1.07 ml/min (median) before remission and 7.93 ml/min after, compared with 8.01 ml/min in the control group. 3. Creatinine clearance (Ccr) increased significantly after remission (63 ml/min to 88 ml/min, P < 0.01), and the fractional excretion of sodium was enhanced. AVP was higher in the nephrotic syndrome both before (2.9 pmol/l) and after remission (2.9 pmol/l) compared with the control group (1.8 pmol/l). ANG II and Aldo did not change after remission and remained at the same level as in the control group. 4. The elevation in ΔCwatermax after remission was accompanied by an increase in Ccr in all patients and ΔCwatermax. and Ccr were significantly correlated (ρ = 0.600, n = 16, P < 0.05). No relationship was found between the change in ΔCwater max. and ANG II and Aldo. 5. AVP was significantly suppressed in patients with nephrotic syndrome before remission, but not after remission nor in control subjects, so that although AVP did not differ in nephrotic patients before and after remission, AVP cannot be excluded as a contributory factor to the reduction in Cwater in the nephrotic syndrome. 6. It is concluded that patients with nephrotic syndrome excrete an oral water load slower than control subjects and that the excretion rate is normal after remission of the syndrome. It is suggested that the normalization of Cwater may be attributed to an increase in glomerular filtration rate or a decrease in proximal tubular sodium reabsorption, although a possible role for AVP has not been excluded.


1977 ◽  
Vol 75 (1) ◽  
pp. 161-172 ◽  
Author(s):  
H. R. BAKKER ◽  
S. D. BRADSHAW

The rate of cutaneous water uptake after dehydration was significantly depressed in functionally neurohypophysectomized toads (Bufo marinas), which consequently regained weight much more slowly than intact toads when returned to water. Toads bearing hypothalamic lesions were able to develop an antidiuresis when removed from water to a saturated atmosphere, but the antidiuresis was solely glomerular in origin and was established more slowly than in intact animals. The fractional reabsorption of filtrate increased significantly and the relative free water clearance decreased significantly in intact toads after removal from water. These changes in tubular function, which were not seen in lesioned toads, were responsible for the development of a more rapid and effective antidiuresis in intact animals. Injections of iso-osmotic saline, oxytocin (250 mu./100 g) and vasopressin (50 mu./100 g) had no significant effect on rates of cutaneous water uptake in both intact and lesioned toads. Injections of hyperosmotic saline, however, significantly increased rates of water uptake in both groups of toads, but to a much greater extent in the intact animals. Fluid retention arising from a marked antidiuresis occurred after the injection of vasopressin and hyperosmotic saline, and there was some evidence of an antidiuretic effect of oxytocin with the doses used here. These results and their bearing on the question of the functional significance of the neurohypophysis in anuran amphibians are discussed.


SLEEP ◽  
2020 ◽  
Vol 43 (Supplement_1) ◽  
pp. A313-A314
Author(s):  
D L Bliwise ◽  
T F Monaghan ◽  
J M Lazar ◽  
M R Epstein ◽  
C W Agudelo ◽  
...  

Abstract Introduction In humans sleeping nocturnally, nocturnal polyuria (NP) refers to high rate of overnight urine production. NP is a heterogeneous condition that may reflect both free water and/or sodium diuresis, but the influence of age on differential fluid handling remains poorly understood. This study examined diuresis rate, sodium clearance, and free water clearance (FWC) by age, time of day (nighttime vs. daytime) and NP status (positive/negative) in subjects under entrained conditions sleeping nocturnally. Methods Convenience samples (age range 18-91; 82 men, 148 women) recruited from a urology ambulatory care unit (n=135) or continence clinic (n=95) collected 8 urine samples at 3-hour intervals over a single 24-hr period. Three separate mixed linear models were constructed for diuresis rate, sodium clearance, and FWC using four predictors: NP status (present [&gt;90mL/h] vs. absent), time of day (night = 0100, 0400, 0700), age (as a continuous measure), and study source. Results Subjects with NP experienced both higher nighttime vs. daytime diuresis rate (1.89 vs. 1.44 mL/min, p&lt;0.001), sodium clearance (0.91 vs. 0.74 mL/min, p&lt;0.001), and FWC (-0.38 vs. -0.71 mL/min, p&lt;0.001), whereas subjects without NP demonstrated lower nighttime vs. daytime diuresis rate (0.94 vs. 1.06, p=0.004) and no difference in sodium clearance (0.59 vs. 0.64, p=0.120) or FWC (-0.80 vs. -0.86, p=0.268). Regardless of NP status, FWC increased with age (p=0.039), and older age (&gt;70) was accompanied by an increase in the ratio of nighttime/daytime diuresis rate and both nighttime and daytime sodium clearance. Conclusion Irrespective of NP, older adults experience proportionally greater nocturnal sodium clearance, as well as a complex surge in both daytime and nighttime FWC. The data imply that both nocturnal sodium clearance and FWC may reflect the relevant substrate underlying excess nocturnal urine production in elderly persons. Support N/A


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