Changes In Arginine Vasopressin Concentrations Research Articles

A copeptin-based classification of the osmoregulatory defects in the syndrome of inappropriate antidiuresis.

Hyponatremia, the most frequent electrolyte disorder, is caused predominantly by the syndrome of inappropriate antidiuresis (SIAD). A comprehensive characterization of SIAD subtypes, defined by type of osmotic dysregulation, is lacking, but may aid in predicting therapeutic success. Here, we analyzed serial measurements of serum osmolality and serum sodium, plasma arginine vasopressin (AVP), and plasma copeptin concentrations from 50 patients with hyponatremia who underwent hypertonic saline infusion. A close correlation between copeptin concentrations and serum osmolality existed in 68 healthy controls, with a mean osmotic threshold±SD of 282±4 mOsM/kg H2O. Furthermore, saline-induced changes in copeptin concentrations correlated with changes in AVP concentrations in controls and patients. With use of copeptin concentration as a surrogate measure of AVP concentration, patients with SIAD could be grouped according to osmoregulatory defect: Ten percent of patients had grossly elevated copeptin concentrations independent of serum osmolality (type A); 14% had copeptin concentrations that increased linearly with rising serum osmolality but had abnormally low osmotic thresholds (type B); 44% had normal copeptin concentrations independent of osmolality (type C), and 12% had suppressed copeptin concentrations independent of osmolality (type D). A novel SIAD subtype discovered in 20% of patients was characterized by a linear decrease in copeptin concentrations with increasing serum osmolality (type E or "barostat reset"). In conclusion, a partial or complete loss of AVP osmoregulation occurs in patients with SIAD. Although the mechanisms underlying osmoregulatory defects in individual patients are presumably diverse, we hypothesize that treatment responses and patient outcomes will vary according to SIAD subtype.

Renal physiology of nocturia.

Renal function, diurnal fluctuations in arginine vasopressin (AVP) secretion, sex, and advanced age affect urine formation and may contribute to nocturia. Renal effects of AVP are mediated by AVP V2 receptors in the kidney collecting duct. Changes in AVP concentration have the greatest relative effects on urine volume when AVP levels are low; therefore small changes can have a large effect on renal water excretion. AVP is the major regulator of water excretion by the kidneys, and AVP levels have been shown to affect nocturnal voiding. Results of several studies show that patients with nocturia had no significant variation in plasma AVP, whereas patients without nocturia had significant diurnal variation in plasma AVP. The V2 receptor gene is located on the X chromosome, which has important sex-specific consequences. For example, mutations in the V2 gene can cause nephrogenic diabetes insipidus, predominantly in men. Age-related changes in water metabolism are associated with overall body composition, kidney, and brain. Older people generally experience decreased extracellular fluid and plasma volume, which leads to increased adverse consequences from net body water gain or loss. Renal function declines with age, and the ability to concentrate urine and conserve sodium is reduced in the elderly. Thirst perception is also decreased in the elderly, who, compared with younger people, tend to hypersecrete AVP in response to higher plasma osmolality, possibly resulting in hyponatremia. These aspects of renal physiology should be considered when antidiuretic drugs are prescribed for the treatment of nocturia.

Comparison of the diuretic effects of medetomidine hydrochloride and xylazine hydrochloride in healthy cats

To investigate dose-related diuretic effects of medetomidine hydrochloride and xylazine hydrochloride in healthy cats. 5 sexually intact cats (4 males and 1 female). The 5 cats received each of 11 treatments. Cats were treated by IM administration of saline (0.9% NaCl) solution (control treatment), medetomidine hydrochloride (20, 40, 80, 160, and 320 μg/kg), and xylazine hydrochloride (0.5, 1, 2, 4, and 8 mg/kg). Urine and blood samples were collected 9 times during a 24-hour period. Variables measured were urine volume, pH, and specific gravity; plasma arginine vasopressin (AVP) concentration; and creatinine and electrolyte concentrations as well as osmolality in both urine and plasma. Both medetomidine and xylazine increased urine production for up to 5 hours after injection. Xylazine had a dose-dependent diuretic effect, but medetomidine did not. Urine specific gravity and osmolality decreased in a dose-dependent manner for both drugs. Free-water clearance increased for up to 5 hours after injection, whereas glomerular filtration rate, osmolar clearance, plasma osmolality, and electrolyte concentrations did not change significantly. Area under the curve for AVP concentrations decreased in a dose-dependent manner for medetomidine but not for xylazine; however, this was not related to diuresis. Both medetomidine and xylazine induced profound diuresis in cats by decreasing reabsorption of water in the kidneys. The diuretic effect of medetomidine, including the change in AVP concentration, differed from that of xylazine. Care must be used when administering these drugs to cats with urinary tract obstruction, hypovolemia, or dehydration.

Plasma Vasopressin Concentrations in Healthy Foals from Birth to 3 Months of Age

Arginine vasopressin (AVP) has received increased attention in equine critical care but there is minimal information of AVP concentration in foals. The clinical usefulness of measuring AVP in ill foals depends on knowledge of age-related changes in AVP concentrations in healthy foals. Plasma AVP concentrations will be significantly different when measured from birth to 3 months of age in healthy foals. Thirteen healthy university-owned foals. Prospective, observational study. Blood was collected from healthy foals at birth and 3, 5, 7, 10, 14, 21, 28, 42, 56, and 84 days of age. Plasma was harvested and plasma AVP concentrations were determined by radioimmunoassay. No statistically significant differences were detected in plasma AVP concentrations over the study period. Plasma AVP concentrations over the entire study period was 6.2+/-2.5 pg/mL. There was no age-related variation in plasma AVP concentrations detected in healthy foals from birth to 3 months of age suggesting that AVP concentrations are similar across foals of these ages.

Only through the brain nuclei, arginine vasopressin regulates antinociception in the rat

The effect of arginine vasopressin (AVP) on rat antinociception was investigated. Intraventricular injection of 50 or 100 ng AVP dose-dependently increased the pain threshold; in contrast, intraventricular injection of 10 μl anti-AVP serum decreased the pain threshold; both intrathecal injection of 200 ng AVP or 10 μl anti-AVP serum and intravenous injection of 5 μg AVP or 200 μl anti-AVP serum did not influence the pain threshold. Pain stimulation reduced AVP concentration in hypothalamic paraventricular nucleus (PVN), and elevated AVP concentration in hypothalamic supraoptical nucleus (SON) and periaqueductal gray (PAG), but no change in AVP concentration was detected in pituitary, spinal cord and serum. The results indicated that AVP regulation of antinociception was limited to the brain nuclei.

Enhanced Ca2+response to AVP in preglomerular vessels from rats with genetic hypertension during different hydration states

Exaggerated arginine vasopressin (AVP)-induced calcium signaling and renal vasoconstriction, characteristic in young spontaneously hypertensive rats (SHR) during euvolemia, are related to greater amounts of V1a receptor mRNA and V1a protein in preglomerular resistance arterioles. The present study determined whether V1a receptor density and calcium signal transduction in the renal vasculature of young SHR is regulated appropriately during physiological changes in hydration state. [3H]AVP ligand binding documented two- to threefold greater density of V1a receptors in euvolemic SHR vs. Wistar-Kyoto (WKY) rats. Parallel changes in V1a receptor density were observed in both strains during chronic water loading (plus approximately 50 fmol/mg) and during dehydration (minus approximately 50 fmol/mg). Affinity was unchanged. Real-time RT-PCR demonstrated that V1a mRNA in preglomerular arterioles was three times greater in euvolemic SHR. Dehydration decreased expression approximately 50% in renal vessels independent of rat strain; water loading increased V1a mRNA. Thus V1a receptor regulation correlated with changes in mRNA in a normal manner in response to chronic changes in AVP concentration, albeit set at a higher level in SHR. In dehydrated animals, AVP increased the cytosolic Ca2+ concentration ([Ca2+]i) by 60 +/- 5 and 112 +/- 13 nM cytosolic Ca2+ in WKY and SHR, respectively (P < 0.01), whereas in hydrated animals the [Ca2+]i increase was 168 +/- 10 and 220 +/- 18 nM, respectively (P < 0.05). In all hydration states, calcium signaling was greater in SHR compared with WKY (P < 0.05). Calcium signaling paralleled changes in the receptor density and mRNA. Mechanisms other than hydration state per se are likely to be responsible for the two- to threefold difference in the V1a receptor density between WKY and SHR in the renal vasculature at the critical age of 6 wk.

Multiple cytosolic calcium signals and membrane electrical events evoked in single arginine vasopressin-stimulated corticotrophs.

The action of arginine vasopressin (AVP) on cytosolic free Ca2+ concentration ([Ca2+]i) was investigated in single rat pituitary corticotrophs using indo-1 microfluorimetry, in part in combination with the monitoring of membrane electrical events with the perforated patch-clamp technique. In corticotrophs showing the series of short-lived [Ca2+]i rises (transient pattern) in response to corticotropin-releasing factor, 100 nM AVP evoked either the transient pattern or a [Ca2+]i spike followed by a sustained plateau (spike/plateau pattern). Not all corticotrophs responded to changes in AVP concentration in the same manner. Some cells exhibited a concentration-dependent increase in [Ca2+]i transient activity, whereas others showing the spike/plateau at high AVP concentrations responded to low agonist concentrations by two [Ca2+]i responses: a slow rising step or two to three sinusoidal-like oscillations. Combined [Ca2+]i and patch-clamp recordings as well as manipulation of extracellular Ca2+ showed that both transient pattern and the plateau of spike/plateau response depended on Ca2+ entry mainly through voltage-gated, dihydropyridine-sensitive Ca2+ channels. By contrast, step, oscillations, and spike were due to Ca2+ release from internal stores. These Ca(2+)-mobilizing responses caused the activation of Ca(2+)-activated, apamin-sensitive K+ channels, which led to a membrane hyperpolarization. These results reveal cell-specific [Ca2+]i signals and associated electrical events in individual AVP-stimulated corticotrophs.

Normalization of plasma arginine vasopressin concentrations when children with meningitis are given maintenance plus replacement fluid therapy

We hypothesized that plasma arginine vasopressin (AVP) concentrations in children with meningitis are appropriate for the children's degree of hypovolemia, even though the concentrations were higher than expected for the serum osmolality. A randomized study was conducted to compare the effect on plasma AVP concentrations of giving maintenance fluid requirements plus replacement of any deficit versus restricting fluids to two thirds of maintenance requirements for 24 hours. Plasma AVP concentrations and serum osmolality were measured before fluid therapy was begun and again after 24 hours. Nineteen children, 2 months to 17 years of age, were studied; 13 had bacterial meningitis (12 with Haemophilus influenzae type b). Ten children (seven with bacterial meningitis) received a mean of 1.42 times the calculated maintenance fluid requirements, and nine (six with bacterial meningitis) were restricted to a mean of 0.65 times maintenance. Children in the maintenance group also received significantly more sodium (mean = 6.3 mEq/kg/24 hr) than children in the fluid-restricted group (mean = 2.0 mEq/kg/24 hr). The two groups were comparable for plasma AVP concentration and serum osmolality before fluid therapy was begun. The plasma AVP concentration was significantly lower after 24 hours of maintenance plus replacement fluids than after fluid restriction (p = 0.005), and the change in AVP concentration correlated with the amount of sodium given (p less than 0.02). This study supports the hypothesis that serum AVP concentrations are elevated in patients with meningitis because of hypovolemia and become normal when sufficient sodium is given to facilitate reabsorption of water by the proximal tubule of the kidney. Patients with meningitis can be given maintenance plus replacement fluids but should be monitored for the development of the syndrome of inappropriate secretion of antidiuretic hormone.

Radioimmunoassay of plasma vasopressin in physiological and pathological states in man.

A radioimmunoassay method for the measurement of arginine-vasopressin (AVP) in human plasma has been developed which requires 5 ml of plasma and has a lower limit of detection of 1-8 pg/ml plasma. Arginine-vasopressin was found to be stable in whole blood for up to 1 h at room temperature and for at least 4 h at 4 degrees C, while in plasma stored at -20 degrees C no loss was seen over 10 days. Dehydration and rehydration in normal subjects produced appropriate changes in AVP concentration but there was considerable variability in the levels attained by individual subjects and no obvious correlation with plasma osmolality. No consistent increase in plasma AVP concentration was seen on change of posture from the recumbent to the upright position. Vigorous exercise produced a marked rise in plasma AVP concentrations in most subjects which could not be attributed simply to an increase in plasma osmolality. In fusion studies with Pitressin in normal subjects showed a mean half-life of 6-4 min with an overall plasma clearance rate of 8-5 ml/min/kg body weight and a mean volume of distribution of 5-33 l. In patients with a biochemical picture suggestive of inappropriate antidiuretic hormone secretion, markedly raised plasma AVP concentrations were found only in patients with bronchial carcinoma.