Antidiuretic effect of perorally administered DDAVP in hydrated humans

In hypothalamic diabetes insipidus, water balance is achieved primarily through the thirst mechanism. The administration of an antidiuretic agent in the drinking water should restore the antidiuretic response to volume and osmoregulatory drive. To test this hypothesis, homozygous Brattleboro strain rats were given arginine vasopressin (AVP) or 1-desamino-8-D-arginine vasopressin (dDAVP) in the drinking water in concentrations of 10–10,000 micrograms/l (AVP) and 5–10,000 micrograms/l (dDAVP). Oral AVP was found to be ineffective. Oral dDAVP resulted in 1) a progressive increase in dDAVP dose, from 2.3 to 2,559 micrograms.day-1.kg-1; 2) a dose-dependent increase in urine osmolality from 306 to 1,796 mosmol/kg; and 3) a dose-dependent decrease in urinary solute excretion. At each dDAVP dose level, stable physiological states were achieved within 24 h. Similar antidiuretic states were achieved when dDAVP was administered in increasing doses or when therapy was initiated at a high dose. These findings demonstrate that inclusion of an appropriate antidiuretic agent in the drinking water can restore the renal response to volume-osmoregulatory drive.

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Effects of a 14-Day Hydration Intervention on Individuals with Habitually Low Fluid Intake

Annals of Nutrition and Metabolism ◽

10.1159/000515375 ◽

2021 ◽

Author(s):

Aaron R. Caldwell ◽

Megan E. Rosa-Caldwell ◽

Carson Keeter ◽

Evan C. Johnson ◽

François Péronnet ◽

...

Keyword(s):

Body Weight ◽

Total Body Water ◽

Fluid Intake ◽

Urine Volume ◽

Urine Osmolality ◽

Body Water ◽

Control Group ◽

Intervention Phase ◽

Total Body ◽

Experimental Group

Background: Debate continues over whether or not individuals with low total water intake (TWI) are in a chronic fluid deficit (i.e., low total body water) [<xref ref-type="bibr" rid="ref1">1</xref>]. When women with habitually low TWI (1.6 ± 0.5 L/day) increased their fluid intake (3.5 ± 0.1 L/day) for 4 days 24-h urine osmolality decreased, but there was no change in body weight, a proxy for total body water (TBW) [<xref ref-type="bibr" rid="ref2">2</xref>]. In a small (n = 5) study of adult men, there were no observable changes in TBW, as measured by bioelectrical impedance, after increasing TWI for 4 weeks [<xref ref-type="bibr" rid="ref3">3</xref>]. However, body weight increased and salivary osmolality decreased indicating that the study may have been underpowered to detect changes in TBW. Further, no studies to date have measured changes in blood volume (BV) when TWI is increased. Objectives: Therefore, the purpose of this study was to identify individuals with habitually low fluid intake and determine if increasing TWI, for 14 days, resulted in changes in TBW or BV. Methods: In order to identify individuals with low TWI, 889 healthy adults were screened. Participants with a self-reported TWI less than 1.8 L/day (men) or 1.2 L/day (women), and a 24-h urine osmolality greater than 800 mOsm were included in the intervention phase of the study. For the intervention phase, 15 participants were assigned to the experimental group and 8 participants were assigned to the control group. The intervention period lasted for 14 days and consisted of 2 visits to our laboratory: one before the intervention (baseline) and 14 days into the intervention (14-day follow-up). At these visits, BV was measured using a CO-rebreathe procedure and deuterium oxide (D2O) was administered to measure TBW. Urine samples were collected immediately prior, and 3–8 h after the D2O dose to allow for equilibration. Prior to each visit, participants collected 24-h urine to measure 24-h hydration status. After the baseline visit, the experimental group increased their TWI to 3.7 L for males and 2.7 L for females in order to meet the current Institute of Medicine recommendations for TWI. Results: Twenty-four-hour urine osmolality decreased (−438.7 ± 362.1 mOsm; p < 0.001) and urine volume increased (1,526 ± 869 mL; p < 0.001) in the experimental group from baseline, while there were no differences in osmolality (−74.7 ± 572 mOsm; p = 0.45), or urine volume (−32 ± 1,376 mL; p = 0.89) in the control group. However, there were no changes in BV (Fig. <xref ref-type="fig" rid="f01">1</xref>a) or changes in TBW (Fig. <xref ref-type="fig" rid="f01">1</xref>b) in either group. Conclusions: Increasing fluid intake in individuals with habitually low TWI increases 24-h urine volume and decreases urine osmolality but does not result in changes in TBW or BV. These findings are in agreement with previous work indicating that TWI interventions lasting 3 days [<xref ref-type="bibr" rid="ref2">2</xref>] to 4 weeks [<xref ref-type="bibr" rid="ref3">3</xref>] do not result in changes in TBW. Current evidence would suggest that the benefits of increasing TWI are not related changes in TBW.

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Contribution of vasopressin to the maintenance of blood pressure during dehydration

AJP Renal Physiology ◽

10.1152/ajprenal.1983.245.5.f615 ◽

1983 ◽

Vol 245 (5) ◽

pp. F615-F621 ◽

Cited By ~ 5

Author(s):

R. L. Woods ◽

C. I. Johnston

Keyword(s):

Blood Pressure ◽

Body Weight ◽

Systolic Blood Pressure ◽

Arginine Vasopressin ◽

Cardiovascular Response ◽

Urine Volume ◽

Brattleboro Rats ◽

Continuous Administration ◽

Plasma Vasopressin ◽

Long Evans

Normal Long-Evans rats, when dehydrated for up to 72 h, have a progressive rise in plasma vasopressin that is associated with a fall in body weight and urine volume, a rise in plasma and urine osmolality, and the maintenance of normal systolic blood pressure. In contrast, Brattleboro diabetes insipidus rats, genetically deficient in vasopressin, when dehydrated to achieve an equivalent body weight loss, have a significant 15 mmHg fall in systolic blood pressure. Even when fluid balance is corrected in the Brattleboro rats by the continuous administration of 1-desamino-8-D-arginine vasopressin, a synthetic vasopressin analogue with potent antidiuretic properties but minimal pressor activity, blood pressure still falls when the animals are dehydrated. In contrast, Brattleboro rats infused with exogenous arginine vasopressin to produce a plasma vasopressin level of 18.9 +/- 3.5 pg X ml-1 are able to maintain normal blood pressure during 48 h of dehydration. This level of vasopressin is comparable to the level found endogenously in dehydrated Long-Evans rats and is nonpressor in normal rats. These results suggest that both the antidiuretic and vasoconstrictor properties of vasopressin are important in the cardiovascular response to dehydration.

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Maternal dehydration-rehydration: fetal plasma and urinary responses

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1988.255.5.e674 ◽

1988 ◽

Vol 255 (5) ◽

pp. E674-E679 ◽

Cited By ~ 2

Author(s):

M. G. Ross ◽

D. J. Sherman ◽

M. G. Ervin ◽

R. Castro ◽

J. Humme

Keyword(s):

Glomerular Filtration Rate ◽

Arginine Vasopressin ◽

Filtration Rate ◽

Urine Volume ◽

Plasma Osmolality ◽

Urine Osmolality ◽

Fetal Plasma ◽

Urine Production ◽

The Impact ◽

Observation Period

Pregnant women may be exposed to exercise, thermal, or gastrointestinal (hyperemesis) water loss, all of which commonly induce a greater than 10 mosmol increase in plasma osmolality. Although fetal osmolality is dependent on maternal osmolality, the impact of maternal dehydration and subsequent maternal rehydration on the fetus has not been explored. Five pregnant ewes with singleton fetuses (136 +/- 1 day) were water deprived for 36 h resulting in a significant increase in plasma osmolality (298 +/- 3.4 to 313 +/- 5.0 mosmol). In response to maternal dehydration, fetal plasma osmolality (297.0 +/- 4.1 to 309.3 +/- 4.1 mosmol), arginine vasopressin (AVP) levels (1.5 +/- 0.2 to 7.9 +/- 1.0 pg/ml), hematocrit (35.1 to 38.6%), and urine osmolality (161.3 +/- 10.7 to 348.9 +/- 21.9 mosmol) significantly increased. Subsequently, ewes were rehydrated over 4 h with intravenously infused 0.45% saline (20 ml.kg-1.h-1). In response to maternal rehydration, maternal and fetal plasma osmolality decreased to basal values (298.9 +/- 3.2 and 300.1 +/- 3.8 mosmol, respectively) and fetal glomerular filtration rate (1.72 +/- 0.30 to 3.08 +/- 0.66 ml/min) and urine volume significantly increased (0.33 +/- 0.02 to 0.71 +/- 0.13 ml/min). However, fetal hematocrit (37.4%), plasma AVP (3.1 +/- 0.9 pg/ml), and urine osmolality (255.4 +/- 28.8 mosmol) did not return to basal levels during the observation period. These results demonstrate fetal hyperosmolality, blood volume contraction, AVP secretion, and altered urine production in response to maternal dehydration. Despite maternal rehydration and normalization of maternal and fetal plasma osmolality, fetal endocrine and fluid responses are prolonged.(ABSTRACT TRUNCATED AT 250 WORDS)

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A vasopressin-mediated diminution of potassium excretion in water-loaded man

Clinical Science ◽

10.1042/cs0690601 ◽

1985 ◽

Vol 69 (5) ◽

pp. 601-606 ◽

Cited By ~ 2

Author(s):

J. Buckley ◽

E. M. Gebruers ◽

W. J. Hall ◽

N. M. B. Harrington

Keyword(s):

Urine Osmolality ◽

Urine Flow ◽

Potassium Excretion ◽

Distal Nephron ◽

Water Diuresis ◽

Specific Effects ◽

Antidiuretic Effect ◽

Endogenous Prostaglandins ◽

Potassium Absorption ◽

Prior Administration

1. Intravenous vasopressin (1–3 μ-units min−1 kg−1) had an antidiuretic effect on water-loaded man and also diminished potassium excretion. As noted by others, aspirin (2.4 g) enhanced the antidiuretic effect of vasopressin, but the fall in potassium excretion was not modified by prior administration of aspirin, which makes it unlikely that the fall was due to the release of endogenous prostaglandins. 2. After terminating the infusion of vasopressin, the fall in potassium output persisted longer than the antidiuresis, which makes it unlikely that the antikaliuretic effect of vasopressin is secondary to its effect on urine flow. 3. The unchanged antikaliuretic effect of vasopressin after aspirin treatment, together with its persistence after terminating the infusion, suggest the possible existence of vasopressin-mediated potassium absorption in the distal nephron in certain circumstances. 4. Aspirin administration had specific effects of its own in water-loaded man. It decreased both the water diuresis and sodium excretion but did not alter potassium excretion or urine osmolality.

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Effect of sodium in a rehydration beverage when consumed as a fluid or meal

Journal of Applied Physiology ◽

10.1152/jappl.1998.85.4.1329 ◽

1998 ◽

Vol 85 (4) ◽

pp. 1329-1336 ◽

Cited By ~ 29

Author(s):

Melinda L. Ray ◽

Mark W. Bryan ◽

Timothy M. Ruden ◽

Shawn M. Baier ◽

Rick L. Sharp ◽

...

Keyword(s):

Weight Loss ◽

Body Weight ◽

Plasma Volume ◽

Urine Volume ◽

Body Weight Loss ◽

Urine Osmolality ◽

Sodium Concentration ◽

Fluid Composition ◽

Liquid Meal ◽

The Impact

To investigate the impact of fluid composition on rehydration effectiveness, 30 subjects (15 men and 15 women) were studied during 2 h of rehydration after a 2.5% body weight loss. In a randomized crossover design, subjects rehydrated with water (H2O), chicken broth (CB: 109.5 mmol/l Na, 25.3 mmol/l K), a carbohydrate-electrolyte drink (CE: 16.0 mmol/l Na, 3.3 mmol/l K), and chicken noodle soup (Soup: 333.8 mmol/l Na, 13.7 mmol/l K). Subjects ingested 175 ml at the start of rehydration and 20 min later; H2O was given every 20 min thereafter for a total volume equal to body weight loss during dehydration. At the end of the rehydration period, plasma volume was not significantly different from predehydration values in the CB (−1.6 ± 1.1%) and Soup (−1.4 ± 0.9%) trials. In contrast, plasma volume remained significantly ( P < 0.01) below predehydration values in the H2O (−5.6 ± 1.1%) and CE (−4.2 ± 1.0%) trials after the rehydration period. Urine volume was greater in the CE (310 ± 30 ml) than in the CB (188 ± 20 ml) trial. Urine osmolality was higher in the CB and Soup trials than in the CE trial. Urinary sodium concentration was higher in the Soup and CB trials than in the CE and H2O trials. These results provide evidence that the inclusion of sodium in rehydration beverages, as well as consumption of a sodium-containing liquid meal, increases fluid retention and improves plasma volume restoration.

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Abstract 308: Nephron Specific Deletion Of Angiotensinogen Modulates Blood Pressure

Hypertension ◽

10.1161/hyp.64.suppl_1.308 ◽

2014 ◽

Vol 64 (suppl_1) ◽

Author(s):

Nirupama Ramkumar ◽

Deborah Stuart ◽

Matias Calquin ◽

Shuping Wang ◽

Fumio Niimura ◽

...

Keyword(s):

Blood Pressure ◽

Drinking Water ◽

Proximal Tubule ◽

Urine Volume ◽

Plasma Renin ◽

Urine Osmolality ◽

Metabolic Balance ◽

Salt Diet ◽

Plasma Renin Concentration ◽

Specific Deletion

It is unknown if intrarenal generation of angiotensinogen (AGT) is important in blood pressure (BP) regulation. Previous studies showed that proximal tubule-specific overexpression of AGT increases BP, while proximal tubule-specific deletion of AGT using the KAP promoter-Cre transgene did not alter BP. The latter study may not have completely eliminated nephron AGT production; in addition, BP was only assessed on a normal salt diet. To evaluate this issue in greater detail, we developed mice with inducible nephron-wide AGT deletion. Mice were generated which were hemizygous for the Pax8-rtTA and LC-1 transgenes and homozygous for loxP flanked AGT alleles to achieve nephron-specific AGT disruption after doxycycline induction. Adult Pax8-rtTA/LC-1/floxed AGT mice at 3 months of age were treated with doxycycline 2 mg/ml in drinking water for 11 days and studied 4 weeks after treatment. Blood pressure (recorded via telemetry) and metabolic balance studies were determined during 5 days of normal, high and low Na diets. Compared to controls, AGT knockout (KO) mice demonstrated significantly lower systolic, diastolic, and mean BPs on all three diets (N=4 each group). The BP reduction was most evident on a low Na diet (mean BP 107 ± 2 mmHg in controls and 88 ± 13 mmHg in AGT KO). Plasma renin concentration was higher in the AGT KO mice as compared to controls on all three diets. There were no detectable differences in weight, urine volume, urine osmolality or urine Na excretion between the controls and KO mice on all three diets, however due to variability, small differences in these parameters may not have been detected. Taken together, these data suggest that nephron AGT may contribute to BP regulation and this is most evident during low Na intake.

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The Acute and Subchronic Toxicity in Rats of Trans-1,2-Dichloroethylene in Drinking Water

Journal of the American College of Toxicology ◽

10.3109/10915818709075692 ◽

1987 ◽

Vol 6 (4) ◽

pp. 471-478 ◽

Cited By ~ 8

Author(s):

J. R. Hayes ◽

L. W. Condie ◽

J. L. Egle ◽

J. F. Borzelleca

Keyword(s):

Drinking Water ◽

Body Weight ◽

Health Hazard ◽

Sprague Dawley ◽

Subchronic Toxicity ◽

Male And Female ◽

Specific Organ ◽

Urinary Parameters ◽

Organ Site ◽

Dose Dependent

Trans-1,2-dichloroethylene was administered either by gavage (acute studies) or in drinking water (subchronic studies) to male and female Sprague-Dawley derived Charles River rats. The acute oral LD50 was 7902 mg/kg for males and 9939 mg/kg for females. Decreased activity, ataxia, and depressed respiration preceded death. In the subchronic study, rats received theoretical daily doses of 500, 1500, and 3000 mg trans-1,2-dichloroethylene/kg body weight/day for 90 consecutive days. The actual daily doses were 402, 1314, and 3114 mg/kg for males and 353, 1257, and 2809 mg/kg for females. There were no compound-related deaths. There were no consistently significant compound-related dose-dependent adverse effects on any of the hematological, serological, or urinary parameters evaluated. There were dose-dependent increases in kidney weights and ratios in treated females. There were no compound-related gross or histological effects. No specific organ site toxicity could be identified in these studies. These data suggest that the toxicity from exposure to trans-1,2-dichloroethylene in drinking water apparently is low and probably does not constitute a serious health hazard.

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Increased PGE2 excretion by dDAVP in humans depends on state of hydration

AJP Renal Physiology ◽

10.1152/ajprenal.1986.250.6.f1008 ◽

1986 ◽

Vol 250 (6) ◽

pp. F1008-F1012 ◽

Cited By ~ 1

Author(s):

U. Schwertschlag ◽

J. G. Gerber ◽

J. S. Barnes ◽

A. S. Nies

Keyword(s):

Water Deprivation ◽

Urine Volume ◽

Plasma Osmolality ◽

Urine Osmolality ◽

Water Diuresis ◽

Water Load ◽

Water Ingestion ◽

Transient Rise ◽

Relationship Of ◽

The Relationship

The relationship of renal prostaglandin E2 (PGE2) excretion (UPGEV) to water deprivation, water diuresis, and subsequent antidiuresis by 1-desamino-8-D-arginine vasopressin (dDAVP) was studied in female volunteers. After 16 h of water deprivation, the subjects began a sustained water diuresis for 8 h. This diuresis caused a transient twofold rise in UPGEV at 2 h (P less than 0.05), which then fell back to or below baseline levels. dDAVP given during the water diuresis caused a transient rise of UPGEV as urine volume decreased and plasma osmolality fell from 277 +/- 1.5 to 271 +/- 2 mosmol/kg (P less than 0.01). Another group of subjects had the water diuresis discontinued after 4 h with dDAVP given at the 5th h when urine volume was decreasing and urine osmolality was increasing. In this setting dDAVP did not produce as great a fall in plasma osmolality nor did it increase UPGEV. These data indicate that renal prostaglandin synthesis (as determined by UPGEV) is increased transiently by an acute water load; dDAVP given during continued water ingestion results in a fall in plasma osmolality and increased PGE excretion; however, dDAVP does not increase UPGEV during normal hydration; and UPGEV is independent of changes in urine flow. These findings imply that renal prostaglandins may have a functional role in humans to inhibit the hydroosmotic actions of antidiuretic hormone, and thus hasten the excretion of a water load, and to prevent overhydration when inappropriate antidiuresis occurs. However, there is no evidence that the stimulus for prostaglandin production is dDAVP per se.

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Continuous ovine fetal hemorrhage: sensitivity of plasma and urine arginine vasopressin response

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1986.251.4.e464 ◽

1986 ◽

Vol 251 (4) ◽

pp. E464-E469 ◽

Cited By ~ 5

Author(s):

M. G. Ross ◽

M. G. Ervin ◽

R. D. Leake ◽

J. A. Humme ◽

D. A. Fisher

Keyword(s):

Blood Volume ◽

Arginine Vasopressin ◽

Urine Volume ◽

Urine Osmolality ◽

Fetal Plasma ◽

Equivalent Rate ◽

Fetal Urine ◽

Ovine Fetus ◽

Ovine Fetal ◽

Fetal Response

Intravascular hemorrhage of the ovine fetus is a potent stimulus for arginine vasopressin (AVP) secretion. However, the method (acute, continuous) and rate of blood withdrawal may influence the fetal response. To determine the hemorrhage threshold for AVP secretion in response to slow continuous hemorrhage, five chronically catheterized ovine fetuses were continuously hemorrhaged (0.6% blood vol/min) to 24-30% blood volume withdrawal. Immediately after hemorrhage fetal blood was reinfused at an equivalent rate. In addition to AVP measurements by radioimmunoassay, fetal urinary responses were monitored as an index of fetal AVP secretion. Significant increases in plasma AVP occurred during hemorrhage (1.0 +/- 0.1 to 8.0 +/- 2.0 pg/ml). The fetal plasma AVP-hemorrhage threshold, as defined by regression analysis, occurred at withdrawal of 13.0% blood volume. Fetal urine volume significantly decreased from a mean basal rate of 0.59 +/- 0.03 to 0.21 +/- 0.06 ml/min at the completion of hemorrhage. Urinary sodium, potassium, and osmolar excretion also significantly decreased at the completion of hemorrhage. Urinary AVP excretion, urine osmolality, sodium, and potassium concentrations did not change significantly during the hemorrhage period but increased significantly during the reinfusion period; the delay a result of renal and catheter dead space. Reinfusion of blood resulted in a return of plasma AVP to basal levels. These results define a threshold for AVP secretion and demonstrate significant urinary effects in response to slow continuous hemorrhage.

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