Osmoregulation Of Vasopressin Secretion Research Articles

Thirst Perception and Osmoregulation of Vasopressin Secretion Are Altered During Recovery From Septic Shock

ObjectiveVasopressin (AVP) secretion during an osmotic challenge is frequently altered in the immediate post-acute phase of septic shock. We sought to determine if this response is still altered in patients recovering from septic shock.DesignProspective interventional studySettingIntensive care unit (ICU) at Raymond Poincaré and Etampes Hospitals.PatientsNormonatremic patients at least 5 days post discontinuation of catecholamines given for a septic shock.InterventionOsmotic challenge involved infusing 500 mL of hypertonic saline solution (with cumulative amount of sodium not exceeding 24 g) over 120 minutes.Measurements and main resultsPlasma AVP levels were measured 15 minutes before the infusion and then every 30 minutes for two hours. Non-responders were defined as those with a slope of the relation between AVP and plasma sodium levels less than < 0.5 ng/mEq. Among the 30 included patients, 18 (60%) were non-responders. Blood pressure and plasma sodium and brain natriuretic peptide levels were similar in both responders and non-responders during the course of the test. Critical illness severity, hemodynamic alteration, electrolyte disturbances, treatment and outcome did not differ between the two groups. Responders had more severe gas exchange abnormality. Thirst perception was significantly diminished in non-responders. The osmotic challenge was repeated in 4 non-responders several months after discharge and the abnormal response persisted.ConclusionMore than half of patients recovering from septic shock have an alteration of osmoregulation characterised by a dramatic decrease in vasopressin secretion and thirst perception during osmotic challenge. The mechanisms of this alteration but also of the relationship between haematosis and normal response remain to be elucidated.

Osmoregulation of vasopressin secretion is altered in the postacute phase of septic shock*

To determine whether septic shock patients have an abnormal reponse to increasing osmolarity. Prospective interventional study. Intensive care unit at Raymond Poincaré and Etampes Hospitals. Normonatremic patients at > 72 hrs from septic shock onset. Osmotic challenge consisting of infusing 500 mL of hypertonic saline solution (with cumulative amount of sodium not exceeding 24 g) over 120 mins. Plasma arginine vasopressin levels were measured 15 mins before the test and then four times every 30 mins. A slope of the relation between arginine vasopressin and plasma sodium levels of < 0.5 pg/mEq defined nonresponders. Among the 33 included patients, 17 (52%) were nonresponders. During osmotic challenge, variations throughout the test in plasma sodium levels, blood pressure, and central venous pressure were comparable between the two groups. Arginine vasopressin increased from 4.8 pg/mL [3.3-6.4 pg/mL] to 14.4 pg/mL [11.2-23.3 pg/mL] in responders but only from 2.8 pg/mL [2.3-4.0 pg/mL] to 4.0 pg/mL [3.1-5.3 pg/mL] in nonresponders (p < .0001). Responders had a higher plasma arginine vasopressin levels at baseline and a more severe hematosis alteration. Nonresponders had more frequently bacteremia and liver dysfunction, been referred from the ward and undergone surgery. Critical illness severity, hemodynamic alteration, hydroelectrolytic disturbances, treatment, and outcome did not differ between the two groups. Osmoregulation is dramatically altered in half of patients with prolonged septic shock.

Autoimmunity to the Sodium-Level Sensor in the Brain Causes Essential Hypernatremia

Na(x) is the sodium-level sensor of body fluids in the brain involved in sodium homeostasis. Na(x)-knockout mice do not stop ingesting salt even when dehydrated. Here we report a case with clinical features of essential hypernatremia without demonstrable hypothalamic structural lesions, who was diagnosed as a paraneoplastic neurologic disorder. The patient had autoantibodies directed against Na(x), along with a ganglioneuroma composed of Schwann-like cells robustly expressing Na(x). The removal of the tumor did not reduce the autoantibody levels or relieve the symptoms. Intravenous injection of the immunoglobulin fraction of the patient's serum into mice induced abnormalities in water/salt intake and diuresis, which led to hypernatremia. In the brains of these mice, cell death was observed along with focal deposits of complement C3 and inflammatory infiltrates in circumventricular organs where Na(x) is specifically expressed. Our findings thus provide new insights into the pathogenesis of hypernatremia relevant to the sodium-level-sensing mechanism in humans.

Osmoregulation of Vasopressin Secretion via Activation of Neurohypophysial Nerve Terminals Glycine Receptors by Glial Taurine

Osmotic regulation of supraoptic nucleus (SON) neuron activity depends in part on activation of neuronal glycine receptors (GlyRs), most probably by taurine released from adjacent astrocytes. In the neurohypophysis in which the axons of SON neurons terminate, taurine is also concentrated in and osmo-dependently released by pituicytes, the specialized glial cells ensheathing nerve terminals. We now show that taurine release from isolated neurohypophyses is enhanced by hypo-osmotic and decreased by hyper-osmotic stimulation. The high osmosensitivity is shown by the significant increase on only 3.3% reduction in osmolarity. Inhibition of taurine release by 5-nitro-2-(3-phenylpropylamino)benzoic acid, niflumic acid, and 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid suggests the involvement of volume-sensitive anion channels. On purified neurohypophysial nerve endings, activation of strychnine-sensitive GlyRs by taurine or glycine primarily inhibits the high K(+)-induced rise in [Ca(2+)](i) and subsequent release of vasopressin. Expression of GlyRs in vasopressin and oxytocin terminals is confirmed by immunohistochemistry. Their implication in the osmoregulation of neurohormone secretion was assessed on isolated whole neurohypophyses. A 6.6% hypo-osmotic stimulus reduces by half the depolarization-evoked vasopressin secretion, an inhibition totally prevented by strychnine. Most importantly, depletion of taurine by a taurine transport inhibitor also abolishes the osmo-dependent inhibition of vasopressin release. Therefore, in the neurohypophysis, an osmoregulatory system involving pituicytes, taurine, and GlyRs is operating to control Ca(2+) influx in and neurohormone release from nerve terminals. This elucidates the functional role of glial taurine in the neurohypophysis, reveals the expression of GlyRs on axon terminals, and further defines the role of glial cells in the regulation of neuroendocrine function.

Osmoregulation of vasopressin secretion in patients with the syndrome of inappropriate antidiuresis associated with central nervous system disorders.

To clarify the characteristics of vasopressin (AVP) secretion in patients with the syndrome of inappropriate antidiuresis (SIAD) related to central nervous system disorders, we examined the response of AVP secretion to osmotic stimulus by hypertonic saline infusion and analyzed the possible causative factors in six patients with SIAD associated with head trauma or cerebral infarction. Hyponatremia developed after head trauma in four patients and cerebral infarction in two patients. In all patients the clinical state and laboratory findings fulfilled the criteria for SIAD, which was supported by either nonsuppressible plasma AVP levels or effectiveness of treatments with water restriction, demeclocycline, nonpeptide V2 AVP antagonist or diphenylhydantoin. Although patterns of plasma AVP response to the osmotic stimulus varied, plasma AVP concentrations neither increased nor decreased to undetectable levels with a rise in plasma osmolality. In one patient, plasma AVP levels responded to increasing plasma osmolality when plasma osmolality normalized; in which the threshold and the sensitivity of osmostat were normal. In two other patients, AVP secretion responded to plasma osmolality after the treatment. The changes in AVP secretion were not due to nonosmotic stimuli for AVP release. In conclusion, this study shows that patients with SIAD and central nervous system disorders may have persistent AVP secretion with a loss of hypotonic suppression such as found in patients with adrenal insufficiency or depletional hyponatremia in central nervous system disorders, indicating that careful evaluation is necessary to determine the relationship between persistent AVP secretion and the pathogenesis of hyponatremic disorders.

Vesicular osmometers, vasopression secretion and aquaporin-4:: A new mechanism for osmoreception?

This review cites new evidence suggesting a link between the recently discovered membrane bound water-selective channel, aquaporin-4 (AQP4), and the mechanism of central osmoreception. AQP4 is found in a number of brain regions associated with the osmoregulation of vasopressin secretion and thirst, including the supraoptic nucleus (SON) and subfornical organ (SFO). AQP4 expression is restricted to ependymal cell membranes in the SFO and astrocyte membranes in the SON, especially perivascular end foot processes, suggesting that glial cells may correspond to Verney’s hypothalamic ‘vesicular osmometers’. Information on osmotic status may thus be conveyed to the neuronal elements of the ‘osmoreceptor complex’ by a neurone–glial interaction.

Hyponatremia and osmoregulation of vasopressin secretion in patients with intracranial bleeding.

To clarify the cause and pathophysiology of hyponatremia after intracranial bleeding, we analyzed the possible causative factors, and examined the response of vasopressin (AVP) secretion to osmotic stimulus in six patients. Despite hyponatremia, urinary sodium excretion persisted, with urinary osmolality exceeding plasma osmolality. Serum levels of urea nitrogen, creatinine, and uric acid were not elevated in any of them. PRA was normal or subnormal in four patients, and all had normal adrenocortical and thyroid functions. Although these laboratory findings may support the diagnosis of the syndrome of inappropriate antidiuretic hormone secretion, the cause of hyponatremia in our patients was attributed to excessive renal excretion of sodium, because water load performed in an euvolemic state showed no impairment in diuresis, and replenishment of sodium without water restriction improved hyponatremia as well as clinical conditions. Plasma AVP levels relative to plasma osmolality in these patients were constantly elevated. When challenged by an osmotic stimulus, AVP secretion increased with increasing plasma osmolality in one patient, but no consistent pattern of AVP secretion was observed in others. The potentiating effect of hypovolemia on osmotic secretion of AVP was not demonstrated in any of the patients. These results show that hyponatremia after intracranial bleeding with clinical features almost indistinguishable from those of syndrome of inappropriate antidiuretic hormone secretion may result from an impaired renal sodium-conserving mechanism of unknown cause. Persistent AVP secretion without an alteration in the sensitivity of the osmostat in this pathological state may be due to an incomplete suppression by plasma hypotonicity per se of the baroreceptor-mediated stimulation of AVP release.

Hyponatremia and osmoregulation of vasopressin secretion in patients with intracranial bleeding

Hyponatremia and osmoregulation of vasopressin secretion in patients with intracranial bleeding

Pitfalls in the Measurement of Plasma Osmolality Pertinent to Research in Vasopressin and Water Metabolism

The reliability of measurements of plasma osmolality is known to be biased by technical artifacts, such as the anticoagulant and the osmometric technique used; the resulting measurement errors therefore may cause errors in interpretation of data. In assessing the potential biasing influence of procedural variables, we found that the temperature at which fresh plasma samples were stored, the duration of storage, and the freezing and thawing of samples appeared to significantly (P < 0.01) affect osmolality values around the narrow physiological range. These factors should be considered in the interpretation of studies on the osmoregulation of vasopressin secretion. In particular, the results suggest that data obtained for any but fresh samples, whether frozen-thawed samples or samples stored at room temperature, are unreliable.

Osmoregulation of vasopressin secretion in the insulin-withdrawn streptozotocin-treated diabetic rat.

To investigate whether hyperglycaemic ketoacidotic diabetic rats continue to osmoregulate the secretion of arginine vasopressin (AVP), male Wistar rats were injected with streptozotocin (150 mg/kg body weight). Rats rendered diabetic were maintained on protamine-zinc insulin (PZI) for 11 days (insulin-treated rats; n = 35), after which PZI was withdrawn for 72 h in half the rats (insulin-withdrawn rats). Insulin-withdrawn and -treated rats were divided into two groups; one was injected i.p. with distilled water (20 ml/kg) and the other with hypertonic saline (500 mmol NaCl/l; 20 ml/kg), and killed 30 min after injection. Insulin-withdrawn rats (water loaded and osmotically stimulated) were hyperglycaemic (16.5 +/- 0.8 and 16.5 +/- 0.9 mmol glucose/l respectively) and ketotic (2077 +/- 664 and 1474 +/- 170 mumol acetoacetate/l respectively). Insulin-treated rats were euglycaemic and non-ketotic. Osmotic manipulation caused similar changes in plasma sodium in both insulin-withdrawn and -treated rats. Plasma AVP was low in the water-loaded rats (0.6 +/- 0.1 and 4.5 +/- 0.9 pmol/l in the insulin-treated and -withdrawn rats respectively) and increased in rats injected with hypertonic saline (1.2 +/- 1.8 and 35.2 +/- 17.9 pmol/l respectively). There was no evidence of hypotension and hypovolaemia in any group of rats. Linear regression analysis defined the functions: plasma AVP = 2.56 (plasma Na-141), r = +0.63, P less than 0.01 for hyperglycaemic ketotic rats; plasma AVP = 0.83 (plasma Na-146), r = +0.78, P less than 0.001 for insulin-treated animals. The slopes and abscissal intercepts were significantly (P less than 0.05) different.(ABSTRACT TRUNCATED AT 250 WORDS)

Osmoregulation of vasopressin secretion and thirst during the estrous cycle of pigs.

The influence of the reproductive cycle on ingestive behaviors, osmotically induced fluid intake, and peripheral blood levels of several hormones involved in fluid electrolyte balance was investigated in young adult female pigs. Food, water, and salt intakes and plasma aldosterone levels were significantly lower during estrus compared with the luteal and follicular phases, whereas plasma sodium (PNa) was higher. Plasma renin activity and lysine vasopressin (LVP) levels did not vary with the cycle. Regression analyses of the relationship between plasma LVP and PNa in unanesthetized, unstressed animals infused for 2 h with intravenous 5% NaCl revealed no significant differences in terms of the osmotic threshold and sensitivity of LVP release at different stages of the reproductive cycle. In contrast, when osmotic loading was carried out with continuous access to water, the osmotic threshold for drinking was found to be significantly higher and the rate of drinking lower during estrus. The results indicate that in the adult female pig the stage of the reproductive cycle has an influence on ingestive behaviors and the osmoregulation of thirst. Osmoregulation of vasopressin secretion, on the other hand, appears to be independent of the estrous cycle in this species.

Osmoregulation of vasopressin secretion and thirst in health and disease.

Osmoregulation of vasopressin secretion and thirst in health and disease.

Vasopressin function in hypercalcaemia.

Vasopressin function and thirst were studied in fourteen hypercalcaemic patients (ten hyperparathyroid and four disseminated malignant disease). Ten patients had decreased renal concentrating ability which reversed within a few days in the majority of patients whose hypercalcaemia was corrected by parathyroidectomy. Although eight patients complained of thirst, none showed a lowered threshold of thirst appreciation during hypertonic saline infusion. Osmoregulation of vasopressin secretion was not reduced in any patient, but the hyperparathyroid group had an exaggerated vasopressin response to osmotic stimulation. We conclude that a partial, reversible nephrogenic diabetes insipidus occurs in at least 70% of hypercalcaemic patients irrespective of cause, which accounts for the polyuria induced by hypercalcaemia.

Vasopressin function in familial cranial diabetes insipidus

A family suffering from cranial diabetes insipidus, that extends over 4 generations, is described. Inheritance of polyuria was autosomal dominant. Vasopressin function was studied in members of the last 2 generations, 4 of whom had polyuria. Osmoregulation of vasopressin secretion was assessed by infusion of hypertonic saline. Plasma vasopressin remained undetectable in one patient, while 2 others had very blunted vasopressin responses to osmotic stimulation. Three non-osmotic stimuli were applied. Controlled hypotension produced by trimetaphan infusion and insulin-induced hypoglycaemia did not increase plasma vasopressin but apomorphine-induced nausea caused a minimal rise in plasma vasopressin to 0.7 pg/ml. Polyuria and thirst resolved with antidiuretic therapy in all patients studied. Congenital absence of vasopressin as in Brattleboro rats is unlikely to account for diabetes insipidus in this disorder since small increases in vasopressin have been demonstrated in these patients. In view of previous post-mortem findings, familial cranial diabetes insipidus is most likely to be due to degeneration of vasopressin-synthesizing neurones.