Vasopressin Secretion In Patients Research Articles

Low-Osmolar Diet and Adjusted Water Intake for Vasopressin Reduction in Autosomal Dominant Polycystic Kidney Disease: A Pilot Randomized Controlled Trial

Autosomal dominant polycystic kidney disease (ADPKD) affects millions of people worldwide. Vasopressin promotes disease progression. A randomized controlled trial with equal (1:1) allocation. This trial examined the effect of combining a low-osmolar (low-sodium [1,500mg/d], low-protein [0.8g per kilogram of body weight]) diet and adjusted water intake on vasopressin secretion in 34 patients with ADPKD. Participants were randomly assigned to receive a low-osmolar diet followed by adjusted water intake to achieve urine osmolality≤ 280mOsm/kg water versus no intervention for 2 weeks. The primary outcome of the study was change (delta) in copeptin levels and urine osmolality between the intervention and control groups from baseline to 2 weeks. Fasting plasma copeptin level, 24-hour urine osmolality, and total solute intake. Baseline characteristics of the 2 groups were similar. Mean plasma copeptin levels and urine osmolality declined from 6.2±3.05 (SD) to 5.3±2.5pmol/L (P=0.02) and from 426±193 to 258±117mOsm/kg water (P=0.01), respectively, in the intervention group compared to a nonsignificant change in the control group (from 4.7±3.6 to 5.07±4pmol/L [P=0.2] and 329±159 to 349±139mOsm/kg water [P=0.3], respectively). The change in copeptin levels (primary outcome) and urine osmolality was statistically significant between the intervention and control groups (delta copeptin,-0.86±1.3 vs+0.39±1.2pmol/L [P=0.009]; delta urine osmolality,-167±264 vs+20±80mOsm/kg water [P=0.007], respectively). Total urinary solute decreased in only the intervention group and significantly differed between groups at week 1 (P=0.03), reducing mean water prescription from 3.2 to 2.6L/d. Small sample size and short follow-up. We developed a stepwise dietary intervention that led to a significant reduction in vasopressin secretion in patients with ADPKD. Furthermore, this intervention led to a reduction in water required for vasopressin reduction.

Smokeless nicotinergic stimulation of vasopressin secretion in patients with persisting nocturnal enuresis and controls.

This study aimed to evaluate the effect of nicotine stimulation on pituitary release of plasma arginine vasopressin (P(AVP)) in patients with primary monosymptomatic nocturnal enuresis (PMNE) and healthy control subjects. Postpubertal teenagers and adult enuretics as well as control subjects were enrolled into the study and admitted to hospital for measurements of P(AVP) in relation to intake of orally administered nicotine. Sixteen patients with PMNE (9 females, 7 males; aged 15-51 years, mean 23.5) and nine normal subjects (4 females, 5 males; aged 24-31 years, mean 27.3) were studied. The enuretics were characterized prior to investigation as either 1-desamino-8-D-arginine vasopressin (DDAVP) responders (n = 8; 16-51 years, mean 28.9) or DDAVP non-responders (n = 8; 15-24 years, mean 18.1) based on the reduction in the number of wet nights. P(AVP), mean arterial blood pressure (MAP) and heart rate (HR) were measured 0, 5, 10, 15 and 30 min, and plasma osmolality (P(osm)) 0 and 30 min after receiving 4 mg nicotine (Nicorette, Pharmacia & Upjohn) chewing gum. In the compiled material a slight but statistically significant increase was observed in P(AVP) at 30 min compared with baseline levels, concurrent with significant rises in MAP and HR above baseline levels at 15 and 30 min. No difference was seen in P(osm) before and after nicotine administration. No other significant variation over time, assessed by an ANOVA, was detected. No difference was encountered in any measured parameter between controls and enuretics or between DDAVP responders and non-responders. Smokeless nicotine chewing gum induces non-osmotic vasopressin release in humans. The secretory AVP capacity to this stimulation is normal in PMNE.

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.

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

Hyponatremia and osmoregulation of thirst and vasopressin secretion in patients with adrenal insufficiency.

To clarify the mechanism underlying abnormal vasopressin (AVP) secretion in glucocorticoid deficiency, we examined the response of AVP secretion to osmotic stimulus produced by 5% saline infusion and analyzed the possible causative factors in seven patients with hypoosmolal hyponatremia resulting from adrenal insufficiency. In all patients, urinary sodium excretion persisted with urine osmolality exceeding plasma osmolality, and plasma AVP levels relative to plasma osmolality were elevated. Blood urea nitrogen, plasma creatinine, and PRA ranged from low to normal. All patients had nausea or vomiting, three had hypotension, and two had hypoglycemia; however, the primary cause of increased AVP secretion was attributed to none of these stimuli. After 5% saline infusion, patterns of changes in plasma AVP levels in individual patients were variable: levels decreased with increasing plasma osmolality in two patients and remained unchanged in the other five patients. Despite hyponatremia and absence of hypovolemia, thirst was present in the five patients, who responded normally to questions. This abnormality in AVP secretion and thirst was corrected after glucocorticoid replacement with normalization of plasma sodium concentrations and osmolality. Thus, glucocorticoid deficiency in man results in a clinical picture almost indistinguishable from that of the syndrome of inappropriate secretion of antidiuretic hormone. Persistent AVP secretion in this pathological state is due to a loss of hypotonic suppression of the osmostat for AVP release, which may be occasioned primarily by glucocorticoid deficiency per se and aggravated secondarily by multiple nonosmotic stimuli including nausea, hypotension, and hypoglycemia.

Hyponatremia and osmoregulation of thirst and vasopressin secretion in patients with adrenal insufficiency

Hyponatremia and osmoregulation of thirst and vasopressin secretion in patients with adrenal insufficiency

Plasma and cerebrospinal fluid measures of arginine vasopressin secretion in patients with bulimia nervosa and in healthy subjects

Plasma and cerebrospinal fluid measures of arginine vasopressin secretion in patients with bulimia nervosa and in healthy subjects

Osmotic and non‐osmotic regulation of thirst and vasopressin secretion in patients with compulsive water drinking

To examine the osmotic and non-osmotic regulation of thirst and AVP release in patients with compulsive water drinking. A 2-hour intravenous infusion of hypertonic (855 mmol/l) sodium chloride solution, followed by a 2-hour drinking period. Seven patients with compulsive water drinking, seven patients with diabetes insipidus and seven healthy controls. Plasma AVP, osmolality, sodium and haematocrit, thirst ratings on a visual analogue scale and the volume of water drunk in 2 hours following infusion. Plasma AVP responses to osmotic stimulation, and non-osmotic inhibition by drinking, were normal in patients with compulsive water drinking. Basal thirst ratings were higher in compulsive water drinking than in either diabetes (P less than 0.001) or controls (P less than 0.001), despite lower basal plasma osmolalities. There was a significant rise in thirst ratings during saline infusion, which correlated closely with plasma osmolality, in all three groups, but the final thirst ratings were higher in compulsive water drinkers, who subsequently drank more water than in either diabetes insipidus (P less than 0.01) or controls (P less than 0.001). Drinking rapidly lowered thirst ratings in controls and diabetes insipidus before changes occurred in plasma osmolality, but remained elevated in patients with compulsive water drinking. Linear regression analysis defined a lower osmotic threshold for thirst in compulsive water drinking compared with controls or diabetes insipidus. There are abnormalities of the osmotic stimulation and non-osmotic inhibition of thirst in compulsive water drinking, suggesting that the underlying defect is one of interpretation of osmotic and non-osmotic inputs. Measurement of thirst responses during hypertonic saline infusion and subsequent water drinking may provide useful diagnostic information in the differentiation of polyuric states.

Hyponatremia and arginine vasopressin secretion in patients with refractory hepatic ascites undergoing peritoneovenous shunting

Seven patients with persistent hyponatremia but normal or elevated serum arginine vasopressin levels and refractory ascites undergoing peritoneovenous shunting were studied in a Metabolic Unit on a 20 mEq sodium 1200 ml fluid-restricted diet to elucidate the mechanism of this response. The intravascular volume expansion after shunt implantation resulted in improvements in cardiac output, renal plasma flow and creatinine clearance (70.7 ± 9.5 to 140.1 ± 18.5 ml/min, p < 0.005). There was an immediate diuresis (632 ± 135 to 2450 ± 323 ml/day, p < 0.005) and natriuresis (3 ± 1 to 25.9 ± 10.6 mEq/24 h, p < 0.05), and urine osmolality decreased significantly (622 ± 91 to 251 ± 76 mosmol/L, p < 0.05) with a significant rise in serum sodium concentration by 72 h (131 ± 2 to 135 ± 1.6 mEq/L, p < 0.05) and serum osmolality. Serum arginine vasopressin levels remained elevated at 3.85 ± 0.94 μU/ml, however, although a transient depression cannot be excluded. Subsequently, a small but significant decrease in serum arginine vasopressin levels to 3.04 ± 0.65 μU/ml (p < 0.05) was associated with a further rise in serum sodium levels above baseline values (138 ±1.4 mEq/L, p < 0.01) and in serum osmolality. In conclusion, these results indicate that in this group of cirrhotic patients with refractory ascites, intrarenal factors, such as decreased delivery of filtrate to the distal nephron as well as elevated inappropriate levels of arginine vasopressin, are important in the pathogenesis of hyponatremia.

Stimulation of ADH release by the renin-angiotensin system.

Stimulation of ADH release by the renin-angiotensin system.