Plasma ADH Research Articles

Effects of vasopressin on carbohydrate metabolism in hepatocytes from dehydrated rats.

AbstractHepatocytes isolated from rats deprived of water for 48 hr (dehydrated) were compared with hepatocytes from control rats with respect to four effects of vasopressin: the inhibition of glucose-promoted glycogen synthesis; the stimulation of glycogenolysis in the absence of exogenous glucose; glucose production; and pyruvate decarboxylation. Vasopressin (ADH) prevented net glycogen synthesis in hepatocytes from both control and dehydrated rats. The inhibitory effect of ADH on hepatocyte glycogen synthesis disappeared within 45 min of washing the cells with hormone-free medium. Vasopressin stimulated glycogenolysis by 60% and glucose output by 80% in hepatocytes from either control or dehydrated rats. In 24-hr-fasted rats, prior dehydration had no effect on either basal or ADH-stimulated glucose production or pyruvate decarboxylation. Thus no evidence was found that water deprivation and the associated prolonged exposure to elevated plasma ADH led to adaptive changes in carbohydrate metabolism or in ...

Influence of mannitol-induced reduction in CSF Na on nervous and endocrine mechanisms involved in the control of fluid balance.

Infusions (20 microliter/min) of isotonic (0.27 M) and hypertonic (0.7 M) mannitol dissolved in Na-free artificial CSF were made for 1 h. into the lateral cerebral ventricle (IVT) of conscious water-replete sheep. The IVT infusion of both 0.27 M and 0.7 M mannitol induced a water-diuresis. Samples of CSF were collected prior to, and 5, 35, 65, 125 min after the end of the infusion. These consistently showed a reduction in CSF [Na], while CSF osmolality remained unchanged after 0.27 M mannitol, and was considerably increased after 0.7 M mannitol. In the 44 dehydrated sheep IVT infusion of 0.7 mannitol in Na-free artificial CSF was made for 6 h. The water deprivation as such caused a marked increase in plasma and CSF [Na] and osmolality. The 6 h IVT infusion of hypertonic mannitol further increased the CSF osmolality, while CSF [Na] decreased and reached a values below the normal for water-replete animals. The infusion also induced a fall in plasma ADH resulting in a water-diuresis, and extinguished the thirst of the dehydrated sheep. Furthermore, the infusion markedly reduced renal sodium excretion with causing any substantial change in blood aldosterone, in spite of the fact that there was a conspicuous increase in plasma renin concentration. The study supports the view that sodium sensitive receptors close to the cerebral ventricular system participate in the regulation of ADH secretion, water intake, renin release, and renal sodium excretion.

Changes in Vasopressin Concentration in Plasma and Cerebrospinal Fluid in Response to Hemorrhage in Anesthetized Dogs

In the anesthetized dog, the concentrations of vasopressin (ADH) in plasma and cerebrospinal fluid (CSF) were similar under basal conditions, and there was a highly significant positive correlation between them (r = 0.71, p less than 0.01). Although hemorrhage was capable of increasing the ADH concentration in both plasma and CSF, the threshold for the increase in plasma ADH was much lower than for the increase in the concentration of ADH in CSF. In addition, the magnitude of the increase in the concentration of ADH in plasma was considerably greater than that in CSF at a comparable degree of hemorrhage. Our results suggest that ADH released into CSF during hemorrhage may have a different origin from that released into blood.

Kallman's syndrom with high set osmotic threshold (OT) and deficient thirst

A patient with Kallman's syndrom is presented, who had deficient thirst mechanism and high set OT for vasopressin secretion. Random determinations of plasma osmolality (Posm) revealed high values of 296-307 mOsm/kg. The OT defined by the isovolemic infusion of hypertonic saline, was 296mOsm/kg. This was significantly higher than the OT of 7 normal controls, 286.6±0.9 (M±SD). He had intact volume receptors, as shown by an appropriate fall of free water clearance during dehydration, from -0.3 to -1.25/min. His pressor receptors were shown to be intact by a normal response to the hypotensive agent trimethaphane with a fall of free water clearance from 10 to 1 ml/min. and a rise of plasma ADH from < 1 to 26uU/ml. Indifference to thirst was expressed at plasma osmolality as high as 301mOsm/kg. It is suggested that deficient thirst and high set OT are additional manifestations of the hypothalamic involvement of Kallman's syndrom.

Stimulation of cardiac receptors with veratrum alkaloids inhibits ADH secretion.

The purpose of this study was to determine whether cardiac receptors that are stimulated by veratrum alkaloids exert an inhibitory influence on the secretion of vasopressin (ADH). In six chloralose-anesthetized dogs, injection of cryptenamine (2 microgram/kg) into the circumflex coronary artery resulted in a significant (P < 0.05) fall in arterial pressure (-45 +/- 5 mmHg). Despite this hypotension and the presence of intact arterial baroreflexes, there was no change in plasma ADH (measured in the superior vena cava). In eight dogs with sinoaortic baroreceptor denervation, hemorrhage of 10 ml/kg decreased arterial pressure 20 +/- 5 mmHg (P < 0.05) and increased plasma ADH from 14 +/- 5 to 38 +/- 13 microU/ml (P < 0.05). Intracoronary injection of cryptenamine (1 microgram/kg) decreased plasma ADH to 23 +/- 7 microU/ml during the 5 min immediately after cryptenamine injection and to 16 +/- 4 microU/ml 20 min after injection. In eight dogs with sinoaortic denervation, hemorrhage and injection of vehicle resulted in a progressive increase in plasma ADH over the same time period. Vagotomy abolished the inhibitory response to cryptenamine injection. These data show that stimulation of cardiac receptors with vagal afferents by intracoronary injection of a veratrum alkaloid inhibits ADH secretion. Activation of these receptors can prevent arterial baroreflex-induced increases in ADH.

Effect of Isoosmolar volume Reduction during Hemofiltration on Plasma Antidiuretic Hormone in Patients with Chronic Renal Failure

The effect of isoosmolar volume reduction on plasma ADH level was studied in 8 patients with chronic renal failure utilizing hemofiltration technique. Plasma ADH fell significantly (P less than 0.001) after one hour of hemofiltration despite volume reduction which was expected to elevate the ADH level. After two hours of hemofiltration, ADH remained low in 5 patients and increased in 3. Post-hemofiltration mean blood pressure was generally lower in patients whose ADH rose than those whose ADH remained low. The two groups were otherwise comparable with respect to total fluid loss, hemofiltration rate, and fluid removed expressed as percent body weight. It can thus be suggested that in these patients a rise in plasma ADH in response to fluid reduction may require a fall in the arterial blood pressure below a critical level. While the rise in plasma ADH observed with continued fluid removal in some patients can be readily explained, we have no clear explanation for the paradoxical initial fall of ADH in all patients and subsequent maintenance of low levels observed in the majority of patients. This unusual ADH response to isoosmolar volume reduction may represent some unidentified mechanism of ADH regulation in patients with end-stage renal disease.

ACTH, ADH, and calcitonin concentrations as markers of response and relapse in small-cell carcinoma of the lung.

The ectopically produced polypeptide hormones ACTH, ADH, and calcitonin were investigated as tumor markers in patients with small-cell carcinoma of the lung (SCC). Plasma ADH concentrations were evaluated separately as well as in relation to concomitantly obtained plasma osmolality levels. No significant nor consistent changes of marker concentrations caused by lysis of tumor cells were found immediately after administration of cytotoxic drugs. After tumor regression, plasma ACTH and serum calcitonin concentrations and inappropriate ADH secretion (plasma ADH levels inappropriately high compared with plasma osmolality) became normal in most cases; however, progressive disease was not followed consistently by changes in plasma ACTH concentrations and occurrence of inappropriate ADH secretion. Contrary to this, among 12 patients with disease progression, serum calcitonin levels increased in ten patients and plasma ADH levels increased in 11 patients. In most cases, however, these changes were only moderate, and serum calcitonin concentrations were found to be increased after tumor regression in patients who had normal pretreatment levels. It is concluded that decisions on treatment of patients with SCC cannot exclusively be based on changes in the concentrations of the polypeptide hormones that might be of ectopic origin.

Assessment of a plasma ADH radioimmunoassay in experimental and physiologic or pathologic conditions.

A radioimmunoassay of ADH has been applied to the study of plasma ADH levels in various conditions. The validity of the assay has been evaluated by the usual quality control parameters of RIA and by the measure of plasma levels in 12 upright water deprived normal volunteers (mean 9.5 pg/ml, SEM +/- 1.5) in 8 resting and hydrated normal volunteers (1.3 +/- 0.4 pg/ml), in a case of diabetes insipidus (1.6 pg/ml), in 8 cases of SIADH Syndrome (range 13-77 pg/ml) and in 4 anesthetized dogs before (33.7 +/- 9.2 pg/ml) and after acute haemorrhage (66 +/- 9.5 pg/ml, p less than 0.02). The osmotoic challenge to ADH secretion has been studied in 8 patients with no overt endocrine pathology by salt perfusion and showed a significant rise (p less than 0.05) of plasma ADH from 6.3 +/- 3.1 pg/ml before, to 20.6 +/- 7.9 pg/ml during salt infusion corresponding to the significant (p less than 0.0001) rise of plasma osmolality from 273 +/- 2.8 to 288.2 +/- 1.1 m Osm/kg.

Failure of acute intravascular volume expansion to alter plasma vasopressin in the nonhuman primate, Macaca fascicularis.

Experiments were carried out in the anesthetized monkey to determine the influence of acute hypervolemia on plasma vasopressin (ADH) concentration. The administration of an isotonic-isooncotic high molecular weight dextran infusion in two steps, each in an amount equal to 15% of the estimated blood volume, produced substantial elevations of left ventricular end diastolic pressure (17.1 cm H2O); however, no consistent change in mean plasma ADH concentration or mean arterial pressure occurred. The results support the position that in the primate, arterial blood pressure rather than blood volume is the major modulator of ADH secretion when blood volume is increased isoosmotically.

Effect of norepinephrine on plasma vasopressin concentration and renal water metabolism.

In the anesthetized, normally hydrated dog, the i. v. infusion of norepinephrine (NE; 0.5 microgram/kg/min) resulted in an increased blood pressure and a marked reduction in the plasma vasopressin (ADH) concentration (2.6 +/- 0.2 to 1.1 +/- 0.2 muU/ml). Urine flow and osmolar clearance, and urine osmolality fell. However, the negative free water clearance (TcH2O) increased, despite the reduction in plasma ADH levels. Thus, the NE-induced diuresis appeared to be due largely to the increased solute excretion, but the reduction in plasma ADH levels may also have been a factor. These data show that change in free water clearance is not a satisfactory index of change in the plasma ADH levels may also have been a factor. These data show that change in free water clearance is not a satisfactory index of change in the plasma ADH concentration when there are acute changes in renal hemodynamics and solute excretion. The norepinephrine-induced reduction in ADH secretion appeared to be due largely to increased activity of the arterial baroreceptors, but a central action cannot be ruled out.

ADH and thermal sweating.

Sweating responses to heat exposure were compared in healthy subjects pretreated with pitressin or alcohol and in the control group. Between the three groups, there were no consistent differences in the rate of sweating expressed both as a total body weight loss during 2-h heat exposure and in mg of sweat per skin area covered by a paper disc. Likewise, there were no differences in the sweat osmolality or electrolyte concentration. There was also no evidence of inverse correlation between plasma ADH level and rate of sweat secretion or its concentration when pooled data of all subjects were analyzed. It was concluded that ADH did not substantially affect thermal sweating in men.

PLASMA ADH LEVELS DURING HEART SURGERY

1) Plasma ADH levels measured by bioassay in the group with extracorporeal circulation were 2.3 +/- 0.6 muu/ml before surgery and 6.6 +/- 1.8 muu/ml during anesthesia. They increased to 196.5 +/- 62.3 muu/ml or about 100 times greater than before surgery during cardiopulmonary bypass. 2) In the group without extracorporeal circulation, plasma ADH levels were 1.5 +/- 0.9 muu/ml before surgery and increased to 44.1 +/- 15.2 muu/ml during operation. 3) After operation decrease in plasma ADH level was relatively rapid in both groups. It became three times that of the control level in the morning of the next day. 4) Marked increase in plasma ADH level during cardiopulmonary bypass was much the same as it was during hemorrhagic shock in dog experiments. 5) Fall in mean arterial blood pressure and loss of pulsatile blood flow will play main roles in this marked increase in ADH during cardiopulmonary bypass through stimulation of arterial baroreceptors and probably chemoreceptors. 6) In two cases with mitral stenosis, increase in plasma ADH during cardiopulmonary bypass was lesser than the other heart diseases.

PLASMA AND URINARY ADH LEVELS IN PATIENTS WITH ESSENTIAL HYPERTENSION

In order to investigate the regulatory system of release and excretion of ADH in essential hypertension, plasma and urinary ADH levels were determined in normal control subjects and patients with essential hypertension. Plasma ADH levels in 42 normal subjects and 53 patients with essential hypertension were 4.5 ± 0.18 pg/ml (mean ± SEM) and 4.0 ± 0.12 pg/ml, respectively, and a significant difference was found between the two groups. Urinary ADH excretion was 74.4 ± 9.5 ng/day (mean ±SEM) and 48.0 ± 8.2 ng/day in 15 normal subjects and in 17 patients, respectively, and it was significantly lower in the patient group. In 25 patients, plasma ADH levels were measured immediately upon admission and after a two week bed rest without medication following admission. A significantly negative correlation was observed between the change of mean blood pressure and plasma ADH levels. After two weeks, sodium restriction (Na : 35 mEq and K : 75 mEq, daily) was ordered for 1 week in 17 patients, and a significant elevation of plasma ADH levels and a remarkable lowering of the blood pressure was found. And there was also a significantly negative correlation between the change of mean blood pressure and plasma ADH levels. Since the linear regression line was steeper after sodium restriction than after a two week rest, the elevation of plasma ADH levels induced by sodium restriction may be considered to be affected not only by the blood pressure lowering but also by the decrease of plasma volume. From these results, it was suggested that the control of ADH release in essential hypertension was maintained normally, and that the baroreceptor might play an important role in regulation of ADH release under these conditions.

Osmometry. 2. Osmoregulation.

The maintenance of osmolar constancy of the body fluids is dependent upon the recognition of osmolar disequilibrium and its correction by modifying the ingestion and excretion of fluid and solute. Osmolar changes are sensed by the hypothalamus which regulates the secretion of antidiuretic hormone to modify the renal excretion of water. The integrity of the system depends upon the renal ability to vary the solute concentration of urine.

Effects of general anaesthesia and surgery on renal function and plasma ADH levels.

Plasma levels of antidiuretic hormone (ADH) were evaluated in 40 adult patients during and after various types of anaesthesia and surgery. The plasma level of ADH increased significantly 30 minutes after the start of anaesthesia with diethyl-ether (3.7 times) and after thiopentone (1.5 times), but it increased insignificantly in neuroleptanaesthesia (2.4 times) and with halothane (1.3 times). The surgical stress evoked marked increases in plasma ADH levels especially at ten minutes after the skin incision. A slight increase in plasma ADH level still continued into the early post-operative days.

1064 CHRONIC HYPONATREMIA AND MIDFACIAL HYPOPLASIA (MFH)

Persistent hyponatremia (Na 126 mEq/L) was found in a 30 month old girl with typical features of MFH. Hyponatremia, serum hypoosmolality (250 mOsm/L), urine hyperosmolality (U/P osm 3:1) and continued urinary sodium excretion suggested the syndrome of inappropriate antidiuretic hormone secretion (SIADH). Renal, adrenal, pulmonary and drug etiologies for SIADH were excluded. 5 mEq/kg hypertonic Na Cl resulted in less than expected rise in serum Na (115 to 120 mEq/L) and marked increase in urine Na excretion (26 to 95 mEq/L). Water loading (25 ml/kg D5W) leading to serum osmolality fall from 250 to 227 mOsm/L or volume expansion (25 ml/kg 0.9% Na Cl iv) did not lead to formation of dilute urine (lowest U osm 686 mOsm/L). Also plasma ADH measured by radioimmunoassay did not fall to 0 (lowest value 1.4 μlU/ml). These findings suggested resistance of hypothalamic center to afferent stimuli from volume and osmoreceptors which normally inhibit ADH release. Only fluid restriction (40 ml/kg/24h) successfully raised serum Na to normal. Serum Na returned to hyponatremic levels on 3 days ad lib diet. MFH has been associated with deficiencies of anterior and posterior pituitary hormones. This report documents persistent ADH excess and further suggests hypothalamic abnormalities in MFH.

Effect of ventriculo-cisternal perfusion with angiotensin II and indomethacin on the plasma vasopressin concentration.

In anesthetized dogs, perfusion of the cerebral ventricles with indomethacin (IM), an inhibitor of prostaglandin biosynthesis, at rates of 1.9 or 7.6 microgram/min was without effect on the plasma ADH concentration. Ventriculo-cisternal perfusion with angiotensin II (AII; 19 ng/min) resulted in a 3-fold increase in the plasma ADH concentration within 45 min. When AII and IM were perfused together, the plasma ADH concentration increased only 2-fold, a response which was significantly lower than that obtained with AII alone. Thus, the ability of central AII to stimulate ADH release may depend, at least in part, upon the local release of prostaglandins.

Antidiuretic hormone levels during cardiopulmonary bypass

The effect of CPB on plasma ADH levels, urine flow, and urine osmolality was studied in nine patients. All patients received morphine, 1 mg. per kilogram, and 50 per cent nitrous oxide-50 per cent oxygen for anesthesia. CPB utilized a Travenol disposable bubble oxygenator and the prime consisted of 3 L. of Ringer's lactate. Measurements were made prior to induction of anesthesia , at 30 minutes following surgical incision, and at 15, 30, and 45 minutes during CPB. There were no statistically significant changes in mean arterial BP, cardiac index, serum sodium, or serum osmolality in any period. Urine flow increased from 0.99 +/- 0.3 ml. per minute to a high of 6.13 +/- 2.0 ml. per minute at 30 minute at 30 minutes on CPB (P less than 0.02). Urine osmolality declined from a control value of 691 +/- 142 mOsm. per kilogram to a low of 425 +/- 48 mOsm. per kilogram at 45 minutes on CPB (p less than 0.05). ADH levels rose from a control value of 4.3 +/- 1.5 to 13.0 +/- 3.3 pg. per milliliter with surgical stimulatiion (p less than 0.05). During CPB the ADH levels rose to a peak of 23.7 +/- 3.6 pg. per milliliter at 30 minutes (p less than 0.01) and were declining at 45 minutes. These data suggest that the stress of CPB results in an outpouring of ADH (or vasopressin) to function as a pressor to produce an increase in peripheral resistance. The ADH concentrations far exceed those required for normal physiologic control of water excretion and the urineflow will thus vary more with the hemodynamic changes than with the ADH levels.

Vasopressin release during ventriculo-cisternal perfusion with prostaglandin E2 in the dog.

In an attempt to determine whether prostaglandin E2 (PGE2) can act centrally to affect the release of vasopressin (ADH), the ventriculo-cisternal system of anaesthetized dogs was perfused with PGE2. When PGE2 was perfused at a rate of 76-4 ng/min (0-19 ml/min), the plasma ADH concentration was unchanged. However, perfusion of PGE2 at a rate of 152-8 ng/min (0-19 ml/min) resulted in a significant increase in the plasma ADH concentration from the control value of 9-0 +/- 2-2 (S.E.M.) to 18-8 +/- 3-9 muu./ml at 10 min and to 41-0 +/- 16-7 muu./ml at 30 min after the start of the perfusion. There were no changes in arterial blood pressure, rectal temperature, plasma osmolality, and the plasma concentrations of sodium and potassium. In additional experiments, i.v. injection of indomethacin (2 or 20 mg/kg) decreased the plasma ADH concentration by approximately 50%. Although this finding is consistent with a role of PGE2 in the control of ADH release, it could also have been due to the observed increases in arterial blood pressure and effective left atrial pressure. Plasma renin activity was unchanged in the indomethacin experiments. It is concluded that PGE2 can act in the central nervous system to stimulate ADH release.

Effects of various ambient temperatures and of heating and cooling the hypothalamus and cervical spinal cord on antidiuretic hormone secretion and urinary osmolality in pigs.

1. Plasma ADH concentration, urinary and plasma osmolality and haematocrit were measured in young pigs placed in cold, thermoneutral, warm and hot ambient temperatures. In some experiments a thermode placed in the hypothalamus or over the cervical spinal cord was heated or cooled at various ambient temperatures. 2. Plasma ADH concentration remained at a low level (0-5--5 muu. ml.-1) over 2 hr or 3 hr periods when the pigs were in cold, thermoneutral or warm ambient temperatures. A hot environment, which caused a marked rise in the pigs' rectal temperature, was associated with a large rise in plasma ADH level. 3. The rise in plasma ADH level which occurred during an increase in body temperature was consistently and completely suppressed by simultaneous cooling of the thermode in the pre-optic region to 5 to 10 degrees C. When the thermode was in the region of the supraoptic nucleus the rise in ADH was only partly suppressed, and when it was over the cervical cord it was only sometimes suppressed. 4. Cooling the thermodes in any position at a cold or thermoneutral ambient temperature, or heating them at a thermoneutral or warm ambient temperature, caused no consistent change in ADH. 5. A diuresis, with a urinary flow-rate of at most 1 ml. min-1 and minimal urinary osmolality of 53 m-osmole kg-1, was observed on only three occasions, twice during cooling of a thermode in the hypothalamus and once after the end of a period when the thermode was heated. In each case, the plasma ADH was less than 2 muu. ml.-1. 6. A slight rise of haematocrit in cold ambient conditions and a slight fall in the warm were observed. Otherwise changes in haematocrit were trivial, and a shift of water between vascular system and interstitium could not be invoked to account for changes in ADH levels. Observed variation of plasma osmolality was also slight.