deamino-arginine-vasopressin and Body-Weight

The treatment of central diabetes insipidus has not changed significantly in recent decades, and dDAVP and replacement of free water deficit remain the cornerstones of treatment. Oral dDAVP has replaced nasal dDAVP as a more reliable mode of treatment for chronic central diabetes insipidus. Hyponatraemia is a common side effect, occurring in one in four patients, and should be avoided by allowing a regular break from dDAVP to allow a resultant aquaresis. Hypernatraemia is less common, and typically occurs during hospitalization, when access to water is restricted, and in cases of adipsic DI. Management of adipsic DI can be challenging, and requires initial inpatient assessment to establish dose of dDAVP, daily fluid prescription, and eunatraemic weight which can guide day-to-day fluid targets in the long-term.

Topics: Body Weight; Deamino Arginine Vasopressin; Diabetes Insipidus; Diabetes Insipidus, Neurogenic; Humans; Hypernatremia; Hyponatremia; Neurophysins; Protein Precursors; Vasopressins

Desmopressin is used for treatment of nocturnal enuresis in children. In this study, we investigated the pharmacokinetics of two formulations-a tablet and a lyophilisate-in both fasted and fed children.. Previously published data from two studies (one in 22 children aged 6-16 years, and the other in 25 children aged 6-13 years) were analyzed using population pharmacokinetic modeling. A one-compartment model with first-order absorption was fitted to the data. Covariates were selected using a forward selection procedure. The final model was evaluated, and sensitivity analysis was performed to improve future sampling designs. Simulations were subsequently performed to further explore the relative bioavailability of both formulations and the food effect.. The final model described the plasma desmopressin concentrations adequately. The formulation and the fed state were included as covariates on the relative bioavailability. The lyophilisate was, on average, 32.1 % more available than the tablet, and fasted children exhibited an average increase in the relative bioavailability of 101 % in comparison with fed children. Body weight was included as a covariate on distribution volume, using a power function with an exponent of 0.402. Simulations suggested that both the formulation and the food effect were clinically relevant.. Bioequivalence data on two formulations of the same drug in adults cannot be readily extrapolated to children. This was the first study in children suggesting that the two desmopressin formulations are not bioequivalent in children at the currently approved dose levels. Furthermore, the effect of food intake was found to be clinically relevant. Sampling times for a future study were suggested. This sampling design should result in more informative data and consequently generate a more robust model.

Topics: Administration, Oral; Adolescent; Antidiuretic Agents; Biological Availability; Body Weight; Chemistry, Pharmaceutical; Child; Cross-Over Studies; Deamino Arginine Vasopressin; Drug Compounding; Fasting; Female; Food; Humans; Male; Models, Biological; Models, Theoretical; Nocturnal Enuresis; Predictive Value of Tests; Tablets; Therapeutic Equivalency

A double-blind, randomized, prospective clinical study was performed to evaluate the efficacy of deamino-8-D-arginin vasopressin in reducing blood loss in major scoliosis surgery.. To evaluate whether desmopressin has any effect on reducing blood loss in spinal surgery, to identify the probable mechanisms of effectiveness via blood coagulation factors, and to outline any adverse effect associated with the use of deamino-8-D-arginin vasopressin.. Scoliosis surgery is known to be associated with major blood loss. Because of major drawbacks of homologous blood transfusion, many alternative methods have been used to counter the blood loss. Only a few studies exist, with controversial results, on the use of deamino-8-D-arginin vasopressin.. The study population included 40 operations on 35 consecutive patients undergoing reconstructive surgery for either idiopathic (n = 26) or congenital (n = 9) scoliosis. Operations were randomized into deamino-8-D-arginin vasopressin (0.3 microgram/kg body weight; maximum, 20 micrograms) (n = 18) or placebo (n = 22) groups and stratified according to the diagnosis and the type of surgery performed (i.e., anterior versus posterior versus anterior and posterior sequential). Parameters of blood loss, serum levels of blood coagulation factors at different time intervals, and urinary output were measured.. Findings indicated that blood loss per kilogram of body weight, blood loss per surgically treated spinal level, urinary output per kilogram of body weight and serum levels of fibrinogen, von Willebrand factor (vWF) activity, tissue type plasminogen activator activity, and plasminogen activator inhibitor activity were not sensitive to the administration of deamino-8-D-arginin vasopressin at any time interval during surgery or at 24 hours after surgery (P > 0.05). Only factor VIII:C levels exhibited significant elevations at 30 minutes and at 24 hours (P < 0.05).. This study could not demonstrate any significant effect of deamino-8-D-arginin vasopressin on the amount of blood loss in a group of patients with idiopathic or congenital scoliosis. Findings indicate that for most of the coagulation factors, any changes in serum levels induced by deamino-8-D-arginin vasopressin were much like those expected from surgery itself. This study also failed to demonstrate any significant effects altering the urinary output that may be attributed to the use of deamino-8-D-arginin vasopressin.

Topics: Adolescent; Blood Coagulation Factors; Blood Loss, Surgical; Body Weight; Deamino Arginine Vasopressin; Diuresis; Double-Blind Method; Female; Hemostatics; Humans; Male; Prospective Studies; Scoliosis; Spinal Fusion; Treatment Outcome

To assess whether desmopressin (1-desamino 8-d-arginine vasopressin) is safe and effective in the treatment of nocturnal polyuria in elderly men.. Twenty men (age 52-80 years) complaining of nocturia were found to have nocturnal polyuria, determined from frequency-volume charts and defined as the production of >33% of the 24 h urine volume overnight, averaged over a 1-week period. In a double-blind study of cross-over design, a 1-week placebo run-in period was followed by two 2-week periods of placebo or 20 microg intranasal desmopressin, and ended with an open 2-week treatment period with 40 microg desmopressin.. Desmopressin caused a significant reduction in nocturnal urine volume and the percentage of urine passed at night, but the reduction in nocturnal frequency was only significant during treatment with 40 microg desmopressin. Four patients on desmopressin experienced side-effects, three of which were thought to be due to fluid retention.. Desmopressin is an effective treatment for nocturnal polyuria in some elderly men. However, it can cause fluid retention and should not be given to patients with cardiac failure. Those undergoing treatment must be closely monitored.

Topics: Aged; Aged, 80 and over; Body Weight; Cross-Over Studies; Deamino Arginine Vasopressin; Humans; Male; Middle Aged; Placebos; Polyuria; Renal Agents; Time Factors; Urine

A series of 22 patients with severe nocturnal enuresis were treated with desmopressin in a randomised double-blind cross-over study. Treatment with 20 and 40 micrograms was highly effective compared with placebo. No difference in dry nights was found between the 2 dosages. Desmopressin proved to be a safe and effective treatment.

Topics: Adolescent; Body Weight; Child; Deamino Arginine Vasopressin; Dose-Response Relationship, Drug; Double-Blind Method; Enuresis; Female; Humans; Male

Day and night urine volume, morning and evening body weight, and supine and sitting blood pressure were measured in five patients with chronic autonomic failure who were not receiving treatment with drugs. All had nocturnal polyuria, overnight weight loss, and a pronounced postural fall in blood pressure, with lowest levels in the morning. Desmopressin (2-4 micrograms given intramuscularly at 8 pm) reduced nocturnal polyuria, diminished overnight weight loss, raised supine blood pressure, and reduced the postural fall, especially in the morning, when patients were often at their worst. Desmopressin may be a useful alternative to, or may supplement, other forms of treatment in some patients with autonomic failure.

Topics: Aged; Autonomic Nervous System Diseases; Body Weight; Deamino Arginine Vasopressin; Female; Humans; Hypotension, Orthostatic; Male; Middle Aged; Polyuria; Potassium; Sodium

Induction of cellular cerebral edema (CE) was achieved by a standard method of water intoxication which consisted of fractionated intraperitoneal administration of distilled water (DW) together with the injection of desmopressin (DP). Using metabolic cage, fluid and food balance was studied in two groups of eight animals: group C - control; group CE - cellular edema induced by water intoxication. For each rat the intake (food pellets and water) and excretion (solid excrements and urine) were recorded for 48 h together with the initial and final body weight. CE animals consumed significantly less food, drank less water and eliminated the smallest amount of excrements. The induction of cellular cerebral edema was accompanied with a significant loss of body weight (representing on average 13 % of the initial values) mainly due to a reduction of food intake. This phenomenon has not yet been reported.

Topics: Animals; Antidiuretic Agents; Body Weight; Brain Edema; Deamino Arginine Vasopressin; Male; Rats; Rats, Wistar; Water Intoxication; Weight Loss

The pharmacokinetics and pharmacodynamics of desmopressin are appropriate for adjusted body weight-based dosing, particularly in obese patients.. The objective of this study was to describe desmopressin dosing strategies, with emphasis on hemostatic outcomes among patients without preexisting bleeding disorders.. This was a single-center, retrospective cohort study of patients who received intravenous weight-based desmopressin for a hemostatic indication. Demographics, comorbidities, treatment setting, indication, site of bleeding, and outcomes were collected from the medical record. Primary outcomes included need for procedural intervention to achieve hemostasis, transfusion requirement, and death. Association between desmopressin dose and outcome was evaluated using χ. A total of 109 patients were included (n = 26, dose adjustment; n = 83, no dose adjustment). Baseline characteristics were well-matched between groups: mean (SD) age of 57.0 (13.5) years; mean (SD) Charlson Comorbidity Score of 6.5 (2.8); 37% were obese; 76% were critically ill; 81% were actively bleeding without differences in site of bleeding; and crude mortality was 39%. No differences in death, mean units of packed red blood cells transfused, or need for procedural hemostasis were observed between adjusted weight- and actual weight-based desmopressin dosing.. When used adjunctively to blood product transfusion in actively bleeding patients, use of adjusted body weight-based desmopressin did not negatively affect clinical outcomes. More data are needed to confirm this dosing strategy.

Topics: Adult; Aged; Blood Coagulation Disorders; Blood Transfusion; Body Weight; Critical Illness; Deamino Arginine Vasopressin; Female; Hemorrhage; Hemostatics; Humans; Male; Middle Aged; Obesity; Retrospective Studies

It has been proposed that a reduction in intracellular calcium causes an increase in intracellular cAMP and PKA activity through stimulation of calcium inhibitable adenylyl cyclase 6 and inhibition of phosphodiesterase 1 (PDE1), the main enzymes generating and degrading cAMP in the distal nephron and collecting duct, thus contributing to the development and progression of autosomal dominant polycystic kidney disease (ADPKD). In zebrafish pde1a depletion aggravates and overexpression ameliorates the cystic phenotype. To study the role of PDE1A in a mammalian system, we used a TALEN pair to Pde1a exon 7, targeting the histidine-aspartic acid dipeptide involved in ligating the active site Zn++ ion to generate two Pde1a null mouse lines. Pde1a mutants had a mild renal cystic disease and a urine concentrating defect (associated with upregulation of PDE4 activity and decreased protein kinase A dependent phosphorylation of aquaporin-2) on a wild-type genetic background and aggravated renal cystic disease on a Pkd2WS25/- background. Pde1a mutants additionally had lower aortic blood pressure and increased left ventricular (LV) ejection fraction, without a change in LV mass index, consistent with the high aortic and low cardiac expression of Pde1a in wild-type mice. These results support an important role of PDE1A in the renal pathogenesis of ADPKD and in the regulation of blood pressure.

Topics: Animals; Blood Pressure; Body Weight; Cardiovascular System; Cyclic AMP; Cyclic Nucleotide Phosphodiesterases, Type 1; Deamino Arginine Vasopressin; Homozygote; Kidney; Mice; Mice, Knockout; Mice, Mutant Strains; Myocardium; Organ Size; Phenotype; Polycystic Kidney, Autosomal Dominant; Proliferating Cell Nuclear Antigen; Transcription Activator-Like Effector Nucleases

Polycystic ovary syndrome (PCOS) is a common condition in women of reproductive age. It is characterized by hyperandrogenism, oligomenorrhea/amenorrhea and polycystic ovaries. It is associated with obesity, diabetes, dyslipidemia and cardiovascular disease. No studies have been conducted on the prevalence of PCOS in Brazilian or South American women. Few studies using the Rotterdam criteria have been published. The objective of the present study was to calculate the prevalence of PCOS at primary healthcare level in Salvador, Brazil based on these criteria.. This was a cross-sectional, two-phase study conducted in a probability sample of women of 18-45 years of age screened for cervical cancer in the primary healthcare network of the city of Salvador, Brazil. In the first phase, interviews were conducted, weight, height, waist circumference, blood pressure and random blood sugar levels were measured, and the presence of acne and hirsutism was investigated. Women with at least one diagnostic criterion were referred for the second phase, which consisted of specialist consultation, pelvic ultrasonography and hormone measurements for differential diagnosis and/or investigation of a second criterion.. Of the 859 women interviewed, 88.5% were black and 58.7% had 11 years of schooling or less. A diagnosis of PCOS was excluded in 84.4%, undetermined in 7.1% and confirmed in 8.5% (95% CI: 6.80-10.56). There were no statistically significant differences between these three groups with respect to weight, body mass index, waist circumference, blood sugar levels or arterial blood pressure. Women with PCOS were younger (p = 0.00), taller (p = 0.04), had fewer children (p = 0.00), were better educated (p = 0.01), and had higher total testosterone levels (p = 0.01) and a higher LH/FSH ratio (p = 0.01).. According to the Rotterdam criteria, the prevalence of PCOS in women seeking primary healthcare in Salvador, Brazil, was 8.5%.

Topics: Acne Vulgaris; Adolescent; Adult; Black People; Blood Glucose; Blood Pressure; Body Height; Body Weight; Brazil; Cross-Sectional Studies; Deamino Arginine Vasopressin; Educational Status; Female; Follicle Stimulating Hormone; Hirsutism; Humans; Middle Aged; Polycystic Ovary Syndrome; Primary Health Care; Testosterone; Waist Circumference; White People

The aim of this study was to examine the effects of desmopressin on morphine withdrawal symptoms and vasopressin level in morphine-dependent subjects.. Wistar male rats were injected s.c. with morphine once per day for 5 consecutive days to induce morphine dependence. After morphine use ceased on day 5, an equal number of rats were assigned to one of four groups for either saline or desmopressin by either intraperitoneal (i.p.) or intracerebroventricular (i.c.v.) injection. From days 5 to 10, urine was collected daily and tested for the presence of morphine, and withdrawal symptoms were monitored to assess the effects of desmopressin.. Significant weight loss occurred among all morphine-addicted rats during the withdrawal period. With both methods (i.p. and i.c.v.), the period of urinary morphine excretion was shorter for the two groups that were given desmopressin (experimental groups) than the two groups that were not given desmopressin (control groups), and no significant difference in urinary morphine excretion was found between the two experimental groups. During the early stage of withdrawal, the severity of the withdrawal symptoms in the experimental groups was significantly lower than that in the control groups.. Desmopressin decreases the extent of morphine withdrawal symptoms, indicating that this agent might be appropriate for treating morphine addiction. Desmopressin appears to reduce withdrawal symptoms not by exerting an anti-diuretic effect but rather by exerting an effect on the central nervous system.

Topics: Animals; Behavior, Animal; Body Weight; Deamino Arginine Vasopressin; Male; Morphine; Morphine Dependence; Rats; Rats, Wistar; Substance Withdrawal Syndrome

Desmopressin is a known haemostatic agent and is also being used, albeit at lower doses, during the diagnostic work-up of Cushing's syndrome, a condition characterized by excess cortisol concentrations and frequent thromboembolic events. No study has yet evaluated whether administration of desmopressin for diagnostic purposes induces significant, adverse changes in endothelial cell markers in these patients.. Administration of desmopressin to patients with Cushing's disease induces changes in endothelial cell markers comparable with those observed in obese and normal weight subjects. It follows, that desmopressin testing does not induce disease-specific untoward changes in coagulatory markers in patients with endogenous hypercortisolism and its use in this context appears safe.. Desmopressin, a vasopressin analogue, is used for various clinical purposes, including haemostasis and, in recent times, the diagnostic work-up of patients with Cushing's syndrome, a condition associated with a known prothrombotic profile. We decided to evaluate whether and to what extent a diagnostic dose of desmopressin induces significant changes in endothelial parameters in patients with Cushing's disease (CD) and obese and normal weight controls.. Twelve patients with CD, 10 obese and five normal weight controls were studied. Von Willebrand antigen (VWF:Ag), tissue plasminogen activator (t-PA) and plasminogen activator inhibitor type 1 (PAI-1) were measured at baseline and up to 4 h after 10 µg desmopressin i.v.. Desmopressin 10 µg transiently increased VWF:Ag and t-PA and decreased PAI-1 in all subjects. The magnitude of the VWF:Ag and t-PA increases after desmopressin was comparable in the three groups (VWF:Ag peak-to-basal ratio 1.9 ± 0.17, 1.5 ± 0.11 and 1.8 ± 0.13 and t-PA peak-to-basal ratio 1.6 ± 0.18, 1.6 ± 0.20 and 1.8 ± 0.24 for CD, obese and controls, respectively, all NS). The PAI-1 decrease observed in patients with CD was comparable with obese (0.7 ± 0.07 and 0.6 ± 0.09, NS) and controls (0.7 ± 0.07 vs. 0.4 ± 0.09, P= 0.08).. Administration of desmopressin to patients with CD for diagnostic purposes induces a transitory increase in VWF:Ag counterbalanced by a decrease in PAI-1 and increase in t-PA. The magnitude of these changes is largely comparable with that observed in obese and normal weight controls. Our data show that testing with desmopressin does not induce disease-specific changes in endothelial markers in patients with CD.

Topics: Body Weight; Case-Control Studies; Deamino Arginine Vasopressin; Fibrinolysis; Humans; Pituitary ACTH Hypersecretion; Plasminogen Activator Inhibitor 1; Tissue Plasminogen Activator; von Willebrand Factor

This study was carried out to investigate the antidiuretic efficacy of 1-desamino-arginine-vasotocin (1-dAVT), 1-desamino-1-monocarba-arginine-vasotocin (1-dlmcAVT) in comparison with desmopressin in Wistar rats. Intramuscular injection of 0.0001 nmole/100 g body weight of desmopressin or synthesized analogues of arginine-vasotocin 5 % in the water loading resulted in significant reduction of urinary flow (p < 0.001) and later removed the diuresis maximum. The most expressed decrease of water excretion which was correlated with the diminished diuresis (r = -0.78,p < 0.001) was observed after injection of 0.0001 nmole/100 g body weight desmopressin. The equivalent increase of water reabsorbtion was induced by 0.00005 nmole/100 g body weight 1-dlmcAVT or desmopressin. The differences between excretion of osmotically active substances, sodium or potassium in the action of 1-dAVT, 1 -d-lmcAVT and desmopressin was not revealed.

Topics: Animals; Antidiuretic Agents; Body Weight; Deamino Arginine Vasopressin; Female; Oxytocics; Potassium; Rats; Rats, Wistar; Sodium; Vasotocin; Water; Water-Electrolyte Balance

Mice lacking AT(1A) receptors for ANG II have a defect in urinary concentration manifested by an inability to increase urinary osmolality to levels seen in controls after thirsting. This defect results in extreme serum hypertonicity during water deprivation. In the basal state, plasma vasopressin levels are similar in wild-type controls and Agtr1a -/- mice. Plasma vasopressin levels increase normally in the AT(1A) receptor-deficient mice after 24 h of water deprivation, suggesting that the defect in urine concentration is intrinsic to the kidney. Using magnetic resonance microscopy, we find that the absence of AT(1A) receptors is associated with a modest reduction in the distance from the kidney surface to the tip of the papilla. However, this structural abnormality seems to play little role in the urinary concentrating defect in Agtr1a -/- mice since the impairment is largely reproduced in wild-type mice by treatment with an AT(1)-receptor antagonist. These studies demonstrate a critical role for the AT(1A) receptor in maintaining inner medullary structures in the kidney and in regulating renal water excretion.

Topics: Angiotensin Receptor Antagonists; Animals; Body Weight; Deamino Arginine Vasopressin; Female; Genotype; Kidney; Kidney Concentrating Ability; Losartan; Male; Mice; Osmolar Concentration; Receptor, Angiotensin, Type 1; Receptors, Angiotensin; Urine; Urodynamics; Vasopressins; Water; Water Deprivation

Aldose reductase (AKR1B1) is the first enzyme in the polyol pathway through which glucose is converted to sorbitol, and has been implicated in the etiology of diabetic complications. However, its physiological role is still not well understood. In the kidney, AKR1B1 is quite abundant in the collecting tubule cells and thought to provide protection against hypertonic environment. We report here that the mice lacking AKR1B1 showed hypercalciuria, hypercalcemia, hypermagnesemia, and reduced ability to concentrate urine, suggesting a new physiological role of AKR1B1 in divalent cation homeostasis.

Topics: Aldehyde Reductase; Animals; Blood Glucose; Blotting, Southern; Blotting, Western; Body Weight; Calcium; Cations; Chlorides; Creatinine; Deamino Arginine Vasopressin; Gene Deletion; Gene Library; Genotype; Glucose; Immunohistochemistry; Kidney; Magnesium; Mice; Mice, Inbred C57BL; Mice, Knockout; Models, Genetic; Phenotype; Phosphates; Potassium; Renal Agents; Sodium; Water; Water Deprivation

The aim of this study was to characterize the magnitude and duration of the antidiuretic effects elicited by desmopressin given in hemostatic dosage intravenously (i.v.) (0.3 microg/kg) or intranasally (i.n.) (300 microg) both as single or repeated doses (four i.n. doses with 12-hr intervals) to healthy volunteers. Urine osmolality increased to a maximum median value of 1,087 mOsmol/kg after the single i.v. dose, 1,065 after the single i.n. dose, and 1,071 during the repeated i.n. dosing schedule, and did not differ significantly between the three dosage schedules. The increase lasted for 24 hr after single doses, and 12 hr after the last of the repeated i.n. doses. Serum sodium did not decrease more than normal diurnal variation after single doses, but decreased marginally below the normal reference range in three volunteers after repeated doses. Lowest median serum sodium concentrations after single i.v. and i.n. doses were 140 and 141 mmol/l, respectively, and 139 after repeated i.n. doses. Body weight changed only marginally after single doses, but increased 1.3 kg during repeated dosing. In adult healthy volunteers, single desmopressin doses give an antidiuretic effect lasting for about 24 hr. There is no difference in magnitude or duration between i.v. or i.n. doses. The effect is prolonged as long as the doses are repeated. Serum sodium is only marginally affected by single doses, but tends to decrease after four repeated doses with 12-hr intervals. If desmopressin is repeated for a period of up to 48 hr, fluid intake should be restricted to 2 liters per day in adults.

Topics: Administration, Intranasal; Adult; Body Weight; Deamino Arginine Vasopressin; Hemostatics; Humans; Injections, Intravenous; Male; Renal Agents; Sodium

We describe a case of diabetes insipidus (DI) due to a pituitary tumor in a 33-year-old pregnant woman who developed a sudden onset of polyuria (over 8 l/day) and polydipsia at 30 weeks of gestation. Her plasma concentration of vasopressin (AVP) was low compared with high serum osmolality (298 mOsm/kg), and her urine output was well controlled by treatment with desmopressin acetate (DDAVP). Cranial magnetic resonance imaging (MRI) demonstrated a 1.8 x 1.2-cm pituitary tumor, but she did not have any disturbance in the release of anterior pituitary hormones. The serum concentration of cystine aminopeptidase (CAP) was within the normal range for a woman at 34 weeks of gestation. After an uncomplicated delivery of a healthy girl, her polyuria gradually resolved. The size of the pituitary tumor gradually decreased in parallel to a reduction in her urine output, but a silent hemorrhage was detected in her pituitary gland 4 weeks after the delivery. Although pregnancy is sometimes associated with central DI, the occurrence of DI due to pituitary tumor under pregnancy is rare. The basal AVP recovered to within the normal range, but the low response of AVP secretion to high osmolality persisted. In this case, pregnancy may affect the manifestation of subclinical DI. This case may therefore enhance our understanding of the mechanisms of DI during pregnancy.

Topics: Adenoma; Adult; Body Weight; Deamino Arginine Vasopressin; Diabetes Insipidus; Female; Humans; Hypoglycemic Agents; Magnetic Resonance Imaging; Osmolar Concentration; Pituitary Function Tests; Pituitary Gland, Anterior; Pituitary Neoplasms; Pregnancy; Pregnancy Complications; Pregnancy Complications, Neoplastic; Pregnancy Trimester, Third; Time Factors; Urine; Vasopressins

To understand the secretion and synthesis of atrial natriuretic peptide we measured immunoreactive atrial natriuretic peptide from plasma, heart tissues and brain areas, and ANP mRNA was determined from heart auricles and ventricles of vasopressin-deficient Brattleboro rats (DI) and from desmopressin treated Brattleboro rats (DI+DDAVP). Long-Evans rats (LE) served as controls. DI+DDAVP rats were given for 3 days sc. injections of 0.5 micrograms 1-desamino-8-D-arginine vasopressin in 1 mL saline twice a day. The rats were housed in single metabolic cages and urinary output and water intake were measured daily. All the body and organ weight parameters were similar in the three groups when the rats were killed. No change was seen in the plasma ANP level between the groups. The right ventricle of DI+DDAVP rats had significantly (P < 0.05) higher concentration of ANP than LE rats (15.8 +/- 4.4 vs. 3.4 +/- 0.6 ng mg-1 tissue). The left ventricle of DI and DI+DDAVP had significantly (P < 0.05) lower amounts of ANP mRNA than LE rats (0.5 +/- 0.2 vs. 1.3 +/- 0.2 and 0.5 +/- 0.1 vs. 1.3 +/- 0.2 arbitrary units). In the hypothalamus, the ANP concentration was significantly (P < 0.05) lower both in DI and in DI+DDAVP rats than in LE rats (9.3 +/- 1.3 vs. 14.5 +/- 1.6 and 6.1 +/- 0.6 vs. 14.5 +/- 1.6 pg mg-1 tissue). To conclude, although the water intake and urinary output of DI rats were changed towards normal with desmopressin treatment, the heart ventricular and hypothalamic ANP did not parallel the change.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Atrial Natriuretic Factor; Body Weight; Brain; Deamino Arginine Vasopressin; Diabetes Insipidus; Drinking; Heart Atria; Heart Ventricles; Hypoglycemic Agents; Male; Myocardium; Organ Size; Rats; Rats, Brattleboro; RNA, Messenger; Urination; Vasopressins; Water-Electrolyte Balance

Rats were infused with a selective agonist of vasopressin V2 receptors (1-desamino-D-arginine vasopressin; DDAVP) at two different doses (1 or 5 ng/h) and fed a liquid formula to produce both moderate (plasma [Na+] = 119-124 mmol/l) and severe (plasma [Na+] = 106-112 mmol/l) hyponatremia. Whole body water and electrolyte contents were analyzed after 1, 7, and 14 days of hyponatremia to assess the relative contributions from water retention and sodium depletion to hyponatremia of varying duration and severity. Body water of the hyponatremic rats was significantly increased over normonatremic control rats after 1 and 7 days; after 14 days, the 1 ng/h DDAVP-infused rats also had elevated body water, but the 5 ng/h DDAVP-infused rats returned to levels not significantly different from controls. Body Na+ and Cl- both decreased significantly after 1 day of hyponatremia, and these decreases were sustained for 14 days; measured decreases were significantly greater in the more hyponatremic rats compared with the less hyponatremic rats. Body K+ of the 1 ng/h DDAVP-infused rats was not different from control rats, but significant K+ decreases occurred in the 5 ng/h DDAVP-infused rats after 7 and 14 days. Analysis of the measured plasma Na+ concentrations vs. those predicted by the changes in body water and sodium showed that both water retention and sodium losses were necessary to predict the final plasma [Na+]. However, the relative contribution from each varied with the duration of induced hyponatremia: acutely, water retention was the major cause of decreased plasma [Na+], but sodium depletion became predominant with longer periods of sustained hyponatremia.

Topics: Animals; Body Water; Body Weight; Chlorides; Deamino Arginine Vasopressin; Disease Models, Animal; Hyponatremia; Inappropriate ADH Syndrome; Male; Potassium; Rats; Rats, Sprague-Dawley; Sodium

The postoperative course of children undergoing surgery for craniopharyngioma was reviewed. Typically they were below height at presentation. All had an attempt at radical surgical resection of the tumor. Most developed diabetes insipidus in the postoperative period, which was permanent in all but 1 child. 94% required thyroid replacement therapy, and sex steroids were administered in 100% when they reached the age of puberty. 91% required maintenance corticosteroids. 54% required growth hormone replacement, but some children showed continued growth despite apparent growth hormone deficiency. Postoperative obesity develops in one half of patients, and may be improved with administration of growth hormone; a controlled trial is underway.

Topics: Adolescent; Body Height; Body Weight; Child; Child, Preschool; Combined Modality Therapy; Craniopharyngioma; Deamino Arginine Vasopressin; Female; Follow-Up Studies; Growth Hormone; Humans; Hypophysectomy; Hypopituitarism; Infant; Male; Pituitary Function Tests; Pituitary Hormones; Pituitary Neoplasms; Postoperative Complications; Thyroxine

The present study proved that desmopressin (DDAVP) (1 microgram DDAVP/12 h/5 días) does not affect ovary, testis and adrenal development in immature Wistar rats (17 days old), because the DDAVP does not modify the weight of the aforementioned organs as compared with the control group. Nevertheless, the male adults Wistar rats (80 days old) showed lower serum testosterone concentrations than the control group, after injection of 4 micrograms/day (2 micrograms/12 h) or 8 micrograms/day (4 micrograms/12 h) of DDAVP during a 5 days period time. Moreover, paradoxical significant lower concentrations of serum testosterone were found in 4 micrograms DDAVP/day-treated rats than in 8 micrograms DDAVP/day-treated ones. The former also showed a decreased number of spermatozoa as compared with the latter and with the control group. The percentage of mobile spermatozoa was lower in rats treated with both concentrations of DDAVP as compared with the control group. Therefore, desmopressin does not delay gonadal and adrenal growth in immature rats, but, at low doses, it affects the testicular function and the mobility of the spermatozoa in male adult rats.

Topics: Adrenal Glands; Age Factors; Animals; Body Weight; Deamino Arginine Vasopressin; Female; Male; Organ Size; Rats; Rats, Wistar; Sperm Motility; Testis

Previous studies have demonstrated that hyponatremia induced by continuous sc infusion of desmopressin (dDAVP) in combination with a liquid diet allows brain volume adaptation with negligible morbidity and mortality in rats. In contrast, some studies of hyponatremia induced by injections of long-acting preparations of arginine vasopressin (AVP) have reported mortality rates as high as 20 to 80%. To evaluate the possibility that the use of AVP to produce antidiuresis may cause greater mortality as a result of increased brain edema, this study examined brain water and electrolyte contents of male and female rats after varying periods of hyponatremia induced by continuous sc infusions of either dDAVP (5 ng/h) or AVP (100 ng/h). Rats infused with AVP had AVP levels in plasma elevated into ranges reported in patients with the syndrome of inappropriate antidiuretic hormone secretion (17.5 +/- 2.0 pg/mL); however, despite the production of comparably severe degrees of hyponatremia with both AVP and dDAVP infusions (105 to 115 mmol/L), no mortality occurred in any of the rats (N = 40 AVP infused and N = 40 dDAVP infused). AVP- and dDAVP-induced hyponatremia both caused transient brain edema in female and male rats, but brain water content returned to the levels of normonatremic controls after 5 days in the females and 10 days in the males. However, at no time during the 10-day study period did brain water content differ significantly between rats infused with AVP or dDAVP, either in females or males. Decreases in brain electrolytes were also equivalent in the AVP- and dDAVP-infused male and female rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Arginine Vasopressin; Body Weight; Brain; Brain Edema; Deamino Arginine Vasopressin; Electrolytes; Female; Hyponatremia; Male; Rats; Rats, Sprague-Dawley; Reference Values; Sodium

Our previous study revealed major ion transport alterations that resulted in a pronounced elevation of red cell Na+ content in DOCA-salt treated homozygous vasopressin-deficient (DI) Brattleboro rats in which only a moderate increase of systolic blood pressure occurred. In contrast, no changes of red cell Na+ content were observed in heterozygous vasopressin-secreting (non-DI) Brattleboro rats with a severe DOCA-salt hypertension. Using a chronic supplementation of DI rats with an antidiuretic agonist dDAVP (1-desamino-8-D-arginine vasopressin) we did not demonstrate any significant changes of red cell ion transport in dDAVP-treated DI rats with a fully developed DOCA-salt hypertension. The absence of ion transport alterations seems to be mainly due to dDAVP-induced correction of altered K+ metabolism seen in DOCA-salt treated DI animals. It can be concluded that DOCA-salt hypertension can develop even without red cell ion transport alterations which are usually caused by cell K+ depletion.

Topics: Animals; Blood Pressure; Body Weight; Deamino Arginine Vasopressin; Desoxycorticosterone; Erythrocytes; Female; Hypertension, Renovascular; Ion Transport; Osmolar Concentration; Potassium; Rats; Rats, Brattleboro; Sodium; Vasopressins

Intranasal desmopressin represents the treatment of choice in Central Diabetes Insipidus. Nevertheless, this route of administration bears some practical disadvantage, linked to either difficult delivering technique, or the status of nasal mucose. The antidiuretic effectiveness of oral desmopressin has been recently demonstrated, both in experimental animals and in man. In our study we compared oral vs. intranasal desmopressin efficacy in 13 patients affected by Central Diabetes Insipidus. The results show that the peroral administration of Desmopressin at a mean dose of 500-600 micrograms/die determines an antidiuretic effect comparable to that of intranasal route, without affecting body weight, arterial pressure and chemical analysis. Side effects, generally limited to the first week of treatment, were described (nausea, vomiting, headache, dizziness [corrected], bitter taste, epygastralgia, asthenia, epystassis), inducing 4/13 patients to withdrawal the trial.

Topics: Administration, Intranasal; Administration, Oral; Adult; Blood Pressure; Body Weight; Deamino Arginine Vasopressin; Diabetes Insipidus; Diuresis; Drug Administration Schedule; Female; Humans; Male; Osmolar Concentration; Specific Gravity

To determine whether the paraventricular nucleus (PVN) contributes to the development of hypertension in spontaneously hypertensive rats (SHR), we compared cardiovascular responses to ganglionic blockade with hexamethonium or vasopressin antagonism with dPVAVP in sham-operated or PVN lesioned SHR and Wistar-Kyoto rats (WKY). Lesions were produced electrolytically when the rats were 5 weeks old. During the next 3 weeks, tail-cuff measurements showed that the development of hypertension in SHR was inhibited, while systolic pressure in WKY was unaffected. Mean pressures recorded directly from the femoral artery at 8 weeks of age were lower in lesioned than in sham-operated SHR (141 +/- 5 vs 110 +/- 3 mm Hg, P less than 0.05), but did not differ in corresponding WKY groups (110 +/- 4 vs 112 +/- 5 mm Hg). Depressor responses to ganglionic blockade induced by i.v. injection of hexamethonium (25 mg/kg) were significantly larger in sham-operated than in lesioned SHR (-41 +/- 4% vs -28 +/- 3%, P less than 0.05). By contrast, vasopressin antagonism with dPVAVP did not alter blood pressure in all rat groups. In 24-h urine samples, excretion of vasopressin was unaffected, but that of norepinephrine was significantly reduced in lesioned SHR. These findings suggest that the PVN contributes to the development of spontaneous hypertension by sympathetic activation without increasing vasopressin secretion.

Topics: Animals; Blood Pressure; Body Weight; Catecholamines; Deamino Arginine Vasopressin; Drinking; Ganglionic Blockers; Heart Rate; Hexamethonium Compounds; Hypertension; Male; Paraventricular Hypothalamic Nucleus; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Sympathetic Nervous System; Vasopressins

Spontaneous manipulator and locomotor activities, food and fluid intake have been recorded from rats suffering from a genetic lack of central vasopressin (VP) synthesis (Brattleboro strain, DI), their heterozygous litter mates (HZ) or Long Evans (LE) rats. The daily patterns of activities did not differ, except for their drinking behavior. This was mainly associated with food intake during the dark period with LE rats but was distributed equally during light and dark periods with DI rats. HZ rats showed a behavioral heterogeneity, some of them following the daily pattern of LE rats, and others, that of DI rats. The daily feeding pattern was identical in the three genotypes but the selection between two isocaloric contrasted diets was different. When they were fed ad lib, HZ and DI rats consumed less carbohydrate than LE rats, the protein intake being unchanged. On the contrary, when the DI rats were only fed during the dark period, they ate more carbohydrate than LE rats. The peripheral infusion of a V2 AVP agonist (dDAVP) restored a normal hydric balance in DI rats but failed to modify the diet selection. These data show that in the rats, the lack of central VP synthesis disturbs both the selection of diets and the efficiency of the satiety signals. These disturbances were unchanged by the peripheral VP treatment which suggested the direct involvement of the central release of the neuropeptide.

Topics: Animals; Arginine Vasopressin; Body Weight; Circadian Rhythm; Deamino Arginine Vasopressin; Dietary Carbohydrates; Dietary Proteins; Drinking; Eating; Hypothalamo-Hypophyseal System; Male; Motor Activity; Oxytocin; Psychomotor Performance; Rats; Rats, Brattleboro; Water-Electrolyte Balance

The vasopressin-mediated recovery of arterial pressure observed in adult rats following pharmacological blockade of the sympathetic nervous and renin-angiotensin systems is reduced by neonatal capsaicin treatment. We now demonstrate a similar but reversible effect following treatment of adult Wistar or Sprague-Dawley rats with N-vanillylnonanamide (50 mg/kg sc). One day after treatment, Wistar, but typically not Sprague-Dawley, rats had lost weight and exhibited increased sensitivity to the anesthetic effects of methohexital sodium. In both strains, captopril treatment caused hypotension. After captopril and ganglionic blockade, vasopressin-mediated recovery of arterial pressure was significantly inhibited. Furthermore, treated Wistar rats had reduced sensitivity to the ocular irritancy of N-vanillylnonanamide when examined 2 days postdose. All deficits reversed within 2 wk of dosing. These data suggest that capsaicin-sensitive systems participate in homeostatic mechanisms engaged during acute hypotension. Because the dose of N-vanillylnonanamide employed in the present study has previously been shown to destroy unmyelinated afferent fibers when administered to adult rats, recovery of the functional deficits may reflect regeneration of damaged processes or assumption of their function by undamaged neurons innervating adjacent sites. By extrapolation from other studies of capsaicin, damage to some central neurons may also be involved.

Topics: Animals; Blood Pressure; Body Weight; Capsaicin; Captopril; Deamino Arginine Vasopressin; Eye; Heart Rate; Hydroxybenzoates; Methohexital; Ocular Physiological Phenomena; Pentolinium Tartrate; Potassium; Rats; Rats, Inbred Strains; Reference Values; Sodium; Species Specificity; Vanillic Acid; Water-Electrolyte Balance

A method for maintaining chronic severe hypoosmolality in rats is described utilizing subcutaneous infusions of the antidiuretic vasopressin analogue 1-deamino-[8-D-arginine] vasopressin (DDAVP) at rates of 1 or 5 ng/hr via osmotic minipumps in combination with self-ingestion of a concentrated, nutritionally-balanced liquid diet. Using these methods, 97.3% of all rats studied achieved stable levels of severe hyponatremia (plasma [Na+] = 111.6 +/- 0.5 mEq/liter, N = 213), which was sustained for periods of time ranging from two to five weeks. Mortality was low (1.8%) and observable morbidity was not noted over a series of studies encompassing 4,628 rat days of sustained hypoosmolality. Analysis of food intake and body weight revealed no evidence of tissue catabolism at any time with the lower (1 ng/hr) DDAVP infusion rate, and only during the first week with the higher (5 ng/hr) rate. Metabolic balance studies during 13 days of sustained hypoosmolality demonstrated the dilutional nature of the hypoosmolality, and only a limited degree of renal escape from the antidiuretic effects of DDAVP (urine osmolalities 800 to 1200 mOsm/kg H2O). Studies of brain water and electrolyte contents demonstrated complete normalization of brain volume after 14 to 28 days of sustained hypoosmolality, the major part of which (70%) could be accounted for by loss of brain electrolytes. Both natriuresis and kaliuresis occurred during the first five days of hypoosmolality, and were of sufficient magnitude to suggest some degree of adaptation of other body fluid compartments via electrolyte losses as well. These results indicate that rats have substantial capacity to tolerate prolonged severe hypoosmolality with little morbidity and mortality as long as proper attention is paid to their nutritional requirements, and provide further evidence that brain volume regulation likely represents the major adaptive mechanism that allows survival despite sustained hypoosmolality.

Topics: Adaptation, Physiological; Animals; Body Water; Body Weight; Brain; Deamino Arginine Vasopressin; Eating; Male; Osmolar Concentration; Rats; Rats, Inbred Strains; Time Factors; Water-Electrolyte Imbalance

Twenty healthy individuals (15 men and 5 women) with initial fasting serum triglycerides greater than or equal to 1.80 mmol/l and euglobulin clot lysis time after venous occlusion greater than or equal to 60 min (upper normal limit 45 min) were tested for fibrinolytic response to venous occlusion and intravenous injection of desmopressin (DDAVP), serum lipids, serum glucose and relative body weight before and after a minimum of 3 to a maximum of 12 months' diet intervention. In order to be defined as a good diet responder, at least 20% reduction of the initial serum triglyceride concentration was required. At the end of the study, half of the participants (7 men and 3 women) met the criteria of good diet responders. All of these showed an improved fibrinolytic response to DDAVP injection, and 7 out of 10 had a normalized fibrinolytic response to venous occlusion. We conclude that, through dietary measures with substantial reduction of hypertriglyceridaemia, it is possible to improve and even normalize the fibrinolytic potential.

Topics: Adult; Blood Glucose; Body Weight; Coronary Disease; Deamino Arginine Vasopressin; Diet; Female; Fibrinolysis; Humans; Male; Prospective Studies; Risk Factors; Triglycerides

We describe three patients who have polydipsia and polyuria due to an abnormality in the osmoregulation of thirst. The clinical manifestations of the syndrome are similar to those of neurogenic diabetes insipidus. Thus, under basal conditions the patients have thirst, normal to high normal levels of plasma osmolality, and low levels of plasma vasopressin. Moreover, antidiuretic therapy greatly reduces thirst and polydipsia as well as polyuria. The only clinically distinguishing feature of the response is that thirst and water intake decrease less rapidly than water excretion. As a consequence, the patients with this syndrome develop variable degrees of dilutional hyponatremia and hypoosmolemia during treatment. The plasma vasopressin response to osmotic stimulation is relatively normal. In most of the patients, the osmotic threshold for vasopressin release is at the upper limit of normal, but this finding only explains their modest elevation in basal plasma osmolality. Thirst and water intake also change as a function of plasma osmolality. However, the threshold or "set" of the thirst osmostat appears to be abnormally low. The degree of downward resetting varies from patient to patient, but is always sufficient to stimulate thirst and water intake at levels of plasma osmolality below the normal range. This abnormality can account not only for the thirst and polyuria under basal conditions but also for the overhydration that occurs during antidiuretic therapy. The pathogenesis of the osmoregulatory abnormality is unknown but may be due to disruption of one or more of the afferent pathways that regulate the "set" of the thirst and vasopressin osmostats.

Topics: Adult; Body Weight; Deamino Arginine Vasopressin; Diabetes Insipidus; Drinking; Female; Humans; Male; Syndrome; Thirst; Urine; Vasopressins; Water-Electrolyte Balance

The separate and combined effects of prenatal protein deficiency (6% casein) and prenatal nitrofen (2,4-dichlorophenyl-p-nitrophenyl ether) exposure (12.5 mg/kg on gestational d 7-21) on renal morphology in the 21-d fetal and postnatal rat were examined. Body weights and kidney weights were reduced in prenatally protein-deprived (PPD) pups at birth and on postnatal day (PND) 10. Numbers of mature glomeruli, creatinine clearance, water diuresis, and response of antidiuretic hormone (ADH), but not the concentrating ability, were lower in the PPD neonates. These changes suggest that prenatal protein deficiency delays renal development and possibly results in a decrease in glomerular clearance and in tubular response to a water load and to antidiuretic hormone. Prenatal nitrofen exposure reduced body weight and kidney size on PND 0 and 10. An increased incidence of hydronephrosis was indicated in the nitrofen-exposed fetus. Prenatal nitrofen exposure depressed the ability to excrete excess water, the response to ADH, and urine-concentrating ability. The functional deficits indicate tubular dysfunction, but little or no effect on glomerular function, as indicated by the absence of an effect on creatinine clearance. Postnatal survival was reduced to 22% by PND in the PPD plus nitrofen pups. Also, prenatal nitrofen exposure increased the susceptibility of the glomeruli in the gestational day (GD) 21 PPD fetus to the adverse effects of prenatal protein deficiency. By PND 10 the toxic effects were of the same order. Renal dysfunction may contribute to the increased mortality in PPD plus nitrofen pups by reducing the ability to respond to stress, but the effects are not sufficiently marked to be considered the primary cause of death.

Topics: Animals; Body Weight; Deamino Arginine Vasopressin; Diuresis; Eating; Female; Herbicides; Kidney; Kidney Concentrating Ability; Litter Size; Organ Size; Phenyl Ethers; Pregnancy; Pregnancy Complications; Protein Deficiency; Rats; Rats, Inbred Strains

Topics: Angiotensin II; Animals; Body Weight; Cardiomegaly; Constriction; Deamino Arginine Vasopressin; Diabetes Insipidus; Diuresis; Drinking; Hematocrit; Hypertension, Renal; Rats; Rats, Brattleboro; Rats, Mutant Strains; Renal Artery; Renin

The effect of a single standard dose of intranasal DDAVP (260 micrograms) was investigated in healthy subjects and in patients with mild deficiencies of VIII:C. Changes in FVIII/VWF activities were measured from baseline after 30, 60, 120 and 360 min of administration of the drug. Intranasal DDAVP was followed by a two-fold increase of VIII:C in both groups studied. VIIIR:AG and VIIIR:RCo increased to a lesser extent. Even though FVIII/VWF activities reached their maximum after 60-120 min, a significant increase over baseline was still observed after 360 min. The rise of VIII:C was unrelated to the body weight of the patients and was proportional to the baseline levels of this factor. In two sisters with combined deficiencies of FV/FVIII, the responses in all activities of FVIII/VWF were similar to those seen in mild hemophiliacs. Factor V did not undergo any variation. No alteration in serum osmolarity and no consistent variation in blood pressure or pulse rate were noted. It is concluded that the i.n. administration of a single high dose of DDAVP might be adopted to provide an emergency aid in bleeding patients with mild to moderate haemophilia A and to yield higher VIII:C levels in blood donors.

Topics: Administration, Intranasal; Adolescent; Adult; Arginine Vasopressin; Blood Coagulation Factors; Body Weight; Deamino Arginine Vasopressin; Factor V Deficiency; Factor VIII; Female; Hemophilia A; Humans; Male; von Willebrand Factor

Topics: Animals; Blood Pressure; Blood Volume; Body Fluids; Body Water; Body Weight; Deamino Arginine Vasopressin; Kidney; Male; Osmolar Concentration; Potassium; Prolactin; Rats; Rats, Inbred Strains; Sodium