Plasma atrial natriuretic peptide: its relationship to changes in sodium intake, plasma renin activity and aldosterone in man

Plasma levels of immunoreactive atrial natriuretic peptide (IrANP), plasma renin activity, aldosterone and vasopressin were measured in 11 normotensive subjects on a low (10 mmol/day), a normal (150 mmol/day) and a high (350 mmol/day) sodium intake. Plasma levels of IrANP increased significantly with increasing dietary sodium intake with levels (means +/- SD) of 3.9 +/- 2.1 pg/ml on the fifth day of the low sodium diet, 6.1 +/- 3.4 pg/ml on the fifth day of the normal sodium diet and 11.4 +/- 4.6 pg/ml on the fifth day of the high sodium diet. Plasma renin activity and aldosterone decreased significantly with increasing sodium intake whereas plasma vasopressin was highest on the high sodium intake. These results suggest that the atrial peptides may be a new and important component in the overall control of sodium and water balance during increased sodium intake.     

Atrial natriuretic peptide inhibits fluid intake in hyperosmolar subjects.

1. The effect of atrial natriuretic peptide on osmotically stimulated thirst appreciation and consequent fluid intake was investigated in healthy man. 2. Six seated male subjects were studied on two occasions: synthetic alpha-human atrial natriuretic peptide (99-126) (2 pmol min-1 kg-1) or placebo (saline, 150 mmol/l NaCl) was infused intravenously for 105 min; 30 min after the start of atrial natriuretic peptide/placebo infusion, hypertonic saline (855 mmol/l NaCl) was infused (0.06 ml min-1 kg-1) for 60 min. Subjects were then allowed free access to water for the next 2 h; infusion of atrial natriuretic peptide/placebo continued for the first 15 min of the drinking period. 3. The plasma atrial natriuretic peptide concentration did not alter significantly during infusion of hypertonic saline and placebo; it rose to a steady state of 12.7 +/- 1.1 pmol/l (mean +/- SEM) during the infusion of atrial natriuretic peptide and hypertonic saline, and remained at this level during the first 15 min of the drinking period. During infusion of hypertonic saline and atrial natriuretic peptide or placebo, similar increases in plasma osmolality (P less than 0.001) and plasma vasopressin concentration (P less than 0.005) occurred. During infusion of hypertonic saline and atrial natriuretic peptide or placebo, thirst increased significantly over the time course of both studies (P less than 0.01), but the effect of atrial natriuretic peptide infusion compared with placebo infusion was to significantly decrease thirst at 60 min. 4. Drinking rapidly abolished thirst and vasopressin secretion before changes in plasma osmolality occurred.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of a single test dose of lithium carbonate on sodium and potassium excretion in man.

1. The possible natriuretic and kaliuretic effects of a single dose of lithium, as used in lithium clearance studies, were investigated in 15 healthy subjects on fixed sodium (100 mmol/24 h) and potassium (70 mmol/24 h) intakes. Lithium carbonate (300 mg or 600 mg) or placebo tablets were administered, double-blind and in random order, midway through a 48 h urine collection (divided into six 8 h periods), at 23.00 hours. 2. During the three 24 h periods which preceded the administration of lithium or placebo (control days), rates of sodium and potassium excretion followed normal circadian patterns, but no differences in excretion rates between the 3 control days were observed. Placebo tablets did not affect excretion rates. 3. After the 300 mg dose of lithium carbonate, 24 h sodium excretion increased by approximately 17 mmol (P less than 0.05); almost all of the natriuretic effect occurred during the first two 8 h periods. No effect on potassium excretion was observed. 4. After the 600 mg dose of lithium carbonate, 24 h sodium excretion increased by approximately 48 mmol (P less than 0.001) and 24 h potassium excretion increased by approximately 19 mmol (P less than 0.01). These effects were confined to the first two 8 h periods and thus occurred before and during the usual lithium clearance period. 5. Plasma renin activity, measured in 10 subjects, increased after the 600 mg dose of lithium carbonate (P less than 0.005), but plasma concentrations of aldosterone and atrial natriuretic peptide were not significantly affected. Neither the 300 mg dose of lithium carbonate nor the placebo tablets affected hormone levels.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of positive and negative pressure breathing on sodium and water excretion

Positive and negative pressure breathing purportedly alter renal sodium and water excretion by modifying hemodynamics and/or hormonal regulators of sodium and water homeostasis. To test this hypothesis we monitored hemodynamic and hormonal responses in seven normal men to (1) continuous positive pressure breathing (19 +/- 1 mm Hg for 30 minutes) after water loading (urine volume = 15 +/- 1 ml/min); and (2) continuous negative pressure breathing (11 +/- 1 mm Hg for 30 minutes) after maintenance water ingestion (urine volume = 4 +/- 1 ml/min), in random order. Each study was repeated on a control day without pressure breathing. Results were as follows (mean +/- SE, p less than 0.05): (1) continuous positive pressure breathing decreased urinary sodium from 0.28 +/- 0.07 to 0.17 +/- 0.04 mEq/min, increased atrial natriuretic peptide from 34.2 +/- 4.9 to 48.5 +/- 6.9 pg/ml, and had no effect on osmolar and free water clearances, cardiac output, plasma renin activity, or plasma aldosterone and plasma arginine vasopressin levels; and (2) continuous negative pressure breathing increased free water clearance from 0.6 +/- 0.7 to 4.5 +/- 1.2 ml/min, urine volume from 4.0 +/- 0.8 to 8.9 +/- 1.3 ml/min, and cardiac output from 5.1 +/- 0.4 to 7.0 +/- 0.6 L/min in a proportional manner (r = 0.40, p less than 0.01) and had no effect on osmolar clearance, urinary volumes of sodium and potassium, plasma renin activity, plasma aldosterone, atrial natriuretic peptide, and arginine vasopressin.(ABSTRACT TRUNCATED AT 250 WORDS)     

Aldosterone, atrial natriuretic factor and sodium intake as determinants of the natriuretic response to head-out water immersion in healthy subjects.

1. The effect of sodium intake on the natriuresis and hormonal changes induced by head-out water immersion was studied in seven normal subjects during head-out water immersion and on a control day while successively on 20 mmol of sodium/day and 100 mmol of sodium/day diets. The effects of head-out water immersion were compared with those seen on the control day for both diets. 2. The natriuresis on the 100 mmol of sodium/day diet was significantly greater than on the 20 mmol of sodium/day diet (natriuretic peak: 10.3 +/- 2.2 versus 3.9 +/- 1 mmol of sodium/h; P less than 0.01). The total sodium excretion during the 3 h of head-out water immersion was 26.2 +/- 2.0 mmol on the 100 mmol of sodium/day diet and 9.9 +/- 0.9 mmol on the 20 mmol of sodium/day diet (P less than 0.01). In contrast, the increase in the plasma atrial natriuretic factor level was similar on both diets (peak plasma atrial natriuretic factor level 23.1 +/- 1.9 versus 26.2 +/- 1 pg/ml; not significant). As expected, the baseline serum aldosterone level was higher on the 20 mmol of sodium/day diet and, despite a significant suppression, remained significantly higher at the end of the third hour of head-out water immersion (peak serum aldosterone level: 495 +/- 130 versus 197 +/- 26 pmol/l, P less than 0.06). Furthermore, there was an inverse relationship between the serum aldosterone level and the urinary sodium excretion at the time of peak natriuresis (r = -0.59, P less than 0.01). 3. We conclude that the effect of sodium intake on the natriuresis induced by head-out water immersion is more dependent upon anti-natriuretic agents, such as aldosterone, than on natriuretic factors, such as atrial natriuretic factor.     

Atrial natriuretic peptide, altitude and acute mountain sickness

1. To investigate the mechanisms of acute mountain sickness, 22 subjects travelled to 3100 m by road and the following day walked to 4300 m on Mount Kenya. Control measurements were made over 2 days at 1300 m before ascent and for 2 days after arrival at 4300 m. These included body weight, 24 h urine volume, 24 h sodium and potassium excretion, blood haemoglobin, packed cell volume, and symptom score for acute mountain sickness. In 15 subjects blood samples were taken for assay of plasma aldosterone and atrial natriuretic peptide. 2. Altitude and the exercise in ascent resulted in a marked decrease in 24 h urine volume and sodium excretion. Aldosterone levels were elevated on the first day and atrial natriuretic peptide levels were higher on both altitude days compared with control. 3. Acute mountain sickness symptom scores showed a significant negative correlation with 24 h urinary sodium excretion on the first altitude day. Aldosterone levels tended to be lowest in subjects with low symptom scores and higher sodium excretion. No correlation was found between changes in haemoglobin concentration, packed cell volume, 24 h urine volume or body weight and acute mountain sickness symptom score. 4. Atrial natriuretic peptide levels at low altitude showed a significant inverse correlation with acute mountain sickness symptom scores on ascent.     

Lack of effect of dietary potassium on renal lithium clearance in man

The effects of alterations in dietary potassium (40, 80 and 160 mmol day-1) on endocrine status and on renal lithium clearance were assessed in 10 healthy subjects on a fixed sodium intake; measurements were made on the fifth day of each dietary regimen. Plasma aldosterone concentration was found to increase with potassium intake, whereas plasma renin activity and the plasma concentration of atrial natriuretic peptide did not change significantly. Neither absolute lithium clearance nor fractional lithium excretion was affected measurably by changes in dietary potassium, suggesting that provided the potassium intake remains within the normal range it is unnecessary to control this factor during lithium clearance studies in man.     

Water depletion, not oral sodium loading, increases levels of sodium, potassium-dependent adenosine triphosphatase inhibitors in rat plasma

In order to define a physiological role for circulating inhibitors of sodium, potassium-dependent adenosine triphosphatase (Na+,K+-ATPase), plasma was obtained from control, water deplete, water repleted, sodium deplete and sodium loaded rats. The effect of this plasma on Na+,K+-ATPase activity, and its transport equivalent 86Rb uptake, was measured in separated guinea pig renal cortical tubules. Plasma from water deplete rats had a raised plasma osmolality and sodium concentration and a significant inhibitory effect on Na+,K+-ATPase (14%) and 86Rb uptake (24%) compared with control or water repleted rats. Inhibition of Na+,K+-ATPase and 86Rb transport was not seen with plasma from rats after dietary sodium loading (urine sodium 5.2 +/- 0.9 mmol/day) compared with low sodium diet controls (urine sodium 0.41 +/- 0.08 mmol/day). Des-amino arginine vasopressin in vivo produced no inhibition of Na+,K+-ATPase or Rb transport. These studies suggest, that in terms of common homoeostatic insults, circulating inhibitors of Na+,K+-ATPase are more responsive to water depletion than to oral sodium loading. The inhibitors may fulfil a physiological role in increasing sodium excretion to maintain osmolality after dehydration.     

Effect of the exercise of seven consecutive days hill-walking on fluid homeostasis.

1. The effect of 7 consecutive days of strenuous exercise, hill-walking, on water balance and distribution was studied in five subjects. The exercise was preceded and followed by 3 control days. The diet was fixed throughout but water was allowed ad libitum. 2. Packed cell volume was measured daily. Serum electrolytes and arginine vasopressin were measured twice daily. Daily water, sodium and potassium balances were calculated. 3. During exercise there was a fall in packed cell volume, reaching a maximum of 11% by day 5 and a retention of sodium reaching a cumulative maximum of 358 mmol by day 6. During and immediately after exercise there was a retention of potassium, reaching a total of 120 mmol by day 3 after stopping exercise. 4. There was a loss of 650 ml of water on day 1 of exercise, followed by a modest retention reaching a cumulative maximum of 650 ml on day 5 of exercise. 5. Neither arginine vasopressin nor serum electrolyte concentrations were affected by exercise. 6. From the packed cell volume, sodium and water balances it was calculated that by day 5 of exercise there was an increase in plasma volume of .068 litre (22%), an increase in interstitial fluid volume of 2.0 litres (17%) and a decrease in intracellular fluid volume of 1.8 litres (8%). 7. These changes, together with the clinical observation of facial and ankle oedema during the experiemnt, suggest that continuous exercise may cause oedema and thus may be a factor in the aetiology of high-altitude oedema.     

Atrial natriuretic factor and changes in dietary sodium intake in patients with chronic renal failure

1. In order to examine the potential role of atrial natriuretic factor in modulating the increased sodium excretion per nephron in chronic renal failure, we studied 12 uraemic patients on the last day of two successive 7 day periods during which their sodium intake was 100 and 20 mmol of sodium/day, respectively. 2. There was a parallel decrease from 6.31 +/- 0.75 to 2.17 +/- 0.32% in the fractional excretion of filtered sodium and from 234.4 +/- 74.9 to 80.6 +/- 20.3 pg/ml (supine position) or 140.1 +/- 43.6 to 60.7 +/- 14.6 pg/ml (upright position) in plasma atrial natriuretic factor. Both parameters were significantly correlated during the two periods of different sodium intake (P less than 0.05). The ratio of plasma guanosine 3':5'-cyclic monophosphate to plasma creatinine changed proportionally to plasma atrial natriuretic factor. Plasma aldosterone and plasma renin activity increased during the sodium-depleted period but only plasma renin activity was significantly correlated with fractional excretion of filtered sodium. 3. The predominant role of atrial natriuretic factor compared with that of aldosterone in the renal response to varying sodium intake is suggested both by regression analysis and by the effect of 5 day's treatment with a converting enzyme inhibitor (enalapril) in six other uraemic patients on a normal (100 mmol/day) sodium intake. Such treatment, although resulting in a significant increase in plasma renin activity and a significant decrease in plasma aldosterone, at least in the supine position, did not modify the fractional excretion of sodium and plasma atrial natriuretic factor.(ABSTRACT TRUNCATED AT 250 WORDS)     

Atrial natriuretic peptide and chronic renal effects of changes in dietary protein and sodium intake in man

1. Plasma levels of atrial natriuretic peptide and several other hormones were measured and related to the renal responses to chronic changes in the dietary intake of protein and sodium, alone and in combination. Eight healthy subjects consumed four diets for 1 week: a basal diet containing 140 mmol of sodium/day and 1 g of protein day-1 kg-1, the same diet with isocaloric addition of 1 g of meat protein day-1 kg-1, the basal diet with addition of 170 mmol of sodium chloride/day and the basal diet with both additions. 2. Creatinine clearance was increased significantly both by protein and, to a smaller extent, by sodium. Plasma atrial natriuretic peptide and the urinary excretion of guanosine 3':5'-cyclic monophosphate were increased significantly by sodium but were not affected by protein. Protein induced a significant rise in plasma glucagon levels, whereas the rise in somatomedin C (insulin-like growth factor I) just failed to reach statistical significance. 3. These findings demonstrate that atrial natriuretic peptide does not mediate chronic protein-induced hyperfiltration, although it may contribute to the renal effects of sodium. Glucagon and somatomedin C (insulin-like growth factor I) may have contributed to chronic protein-induced hyperfiltration.     

Changes in the plasma levels of atrial natriuretic peptides during mineralocorticoid escape in man

Plasma levels of atrial natriuretic peptide (ANP) were measured by radioimmunoassay in eight normal healthy volunteers before and during mineralocorticoid escape. Mean plasma ANP on a fixed sodium intake before fludrocortisone was 6.5 +/- SEM 1.1 pg/ml. Within 24 h of fludrocortisone administration there was a significant increase in plasma ANP which continued to increase daily reaching a plateau by day 4 (14.9 +/- 2.4 pg/ml) to day 7 (15.1 +/- 2.6 pg/ml). The rise in plasma ANP was closely related to the amount of sodium retained during the fludrocortisone treatment and the sodium 'escape' occurred by days 4 to 7. These results support the concept that ANP could play an important hormonal role in over-coming the sodium-retaining effects of mineralocorticoids in man.     

Diurnal and postural variations in plasma atrial natriuretic factor, plasma guanosine 3':5'-cyclic monophosphate and sodium excretion

1. We studied diurnal patterns of plasma atrial natriuretic factor, plasma guanosine 3':5'-cyclic monophosphate and urinary sodium excretion in normal subjects after 3 days on a 200 mmol of sodium/60 mmol of potassium diet. On the fourth day blood samples and urine were collected every 3 h. 2. Two studies were performed. In study 1, normal subjects (n = 8) were recumbent for 23 h from 09.00 hours to 08.00 hours the next day. In study 2, normal subjects (n = 10) were permitted to ambulate from 09.00 hours to 23.00 hours and then were recumbent until 08.00 hours the next day. 3. In study 1, assumption of the recumbent posture was associated with increases in plasma atrial natriuretic factor (P less than 0.01), plasma guanosine 3':5'-cyclic monophosphate (P less than 0.05) and urinary sodium excretion (P less than 0.05). 4. In contrast, in study 2 there were no significant changes in plasma atrial natriuretic factor during the day; instead, plasma atrial natriuretic factor increased overnight, reaching a peak at 24.00 hours after 1 h of recumbency (P less than 0.01). A smaller rise in plasma guanosine 3':5'-cyclic monophosphate (P less than 0.05) occurred; urinary sodium excretion decreased markedly (P less than 0.01) and there was no change in creatinine clearance. 5. In both studies, recumbency was associated with an initial drop, followed by a rise, in packed cell volume. 6. These data demonstrate that assumption of the supine position induces a rise in plasma atrial natriuretic factor and accounts for most of the observed variation.(ABSTRACT TRUNCATED AT 250 WORDS)     

The influence of streptozotocin-induced diabetes mellitus on fluid and electrolyte handling in rats

Intakes and urine outputs of fluid and electrolytes were measured daily in rats before, and for 3 weeks after, induction of diabetes by intraperitoneal injection of streptozotocin (STZ; 60 mg/kg); control animals received saline. Water intakes and urine outputs were increased on and after the first day after injection with STZ; after a transient period of negative water balance, fluid intakes and urine outputs increased in parallel. Food intake was reduced for the first 3 days after injection of STZ but thereafter there was a steady increase. On the final experimental day, the food intake of the diabetic group was 60% greater than that of the control group. Urinary electrolyte excretion was increased after injection of STZ; at the end of the experiment, the increase in urinary sodium excretion was similar to the increase in intake but the increase in urinary potassium excretion was less. On day 21 after injection of STZ plasma sodium concentration and packed cell volume were significantly reduced in the diabetic group but plasma potassium concentration was not. There was a difference between the measured osmolality and the calculated osmolarity of the plasma of the diabetic animals which was not seen in the controls. This difference was not due to pseudohyponatraemia, but was probably due to the presence of unidentified solutes, since there was a significant gap between the urinary osmolal and osmolar excretion in the diabetic animals that was not present in the control animals.     

Atrial natriuretic peptide inhibits osmolality-induced arginine vasopressin release in man

1. Eight normal volunteers were infused with 5% saline (5 g of NaCl/100 ml) at a rate of 0.06 ml min-1 kg-1 for 120 min to increase plasma osmolality and plasma arginine vasopressin. Human atrial natriuretic peptide (alpha-hANP; 100 micrograms) or placebo was given in random order in a double-blind cross-over design for the last 20 min of the saline infusion. 2. Compared with the placebo infusion, atrial natriuretic peptide (ANP) produced a 43% greater sodium excretion and a 34% greater urinary volume in the subsequent hour. 3. Mean plasma immunoreactive ANP did not increase in response to changes in osmolality and rose to a peak of 118 pg/ml during the alpha-hANP infusion. alpha-hANP produced significant suppression of mean plasma arginine vasopressin over the 60 min after the infusions. 4. We conclude that ANP is not released in response to increased osmolality in vivo, and that it inhibits osmolality-induced arginine vasopressin release in man.     

The effect of water abstention on milk synthesis in lactating women

The effects of dehydration on mechanisms of water balance and milk synthesis were investigated in ten lactating Gambian women who were fasting during Ramadan. Ten non-pregnant, non-lactating women acted as controls. Fasting consisted of total water abstention from 05.00 hours to 19.30 hours and was accompanied by high insensible water losses. Lactating women lost 7.6% of their total body water between 07.00 hours and 19.00 hours. Control subjects lost significantly less. Plasma indices of dehydration (osmolality, sodium, uric acid) showed a greater rise in the lactating women than in the control subjects over the period of fasting. However, the 19.00 hours values remained in the normal range obtained on non-Ramadan days. During Ramadan the lactating women restricted their urinary output to a lesser degree than the controls, and for much of the day their urine was also less concentrated. The lactating women appeared to have adapted by superhydrating themselves overnight. This resulted in very low urine concentrations (osmolality, sodium, urea, creatinine) in morning samples. Urine concentrations approached, but did not exceed, non-Ramadan levels by late afternoon. The daily water turnover of 6.4 litres in the lactating women was 2 litres greater than in the controls. This difference was much greater than that required for milk synthesis (500 ml) and may represent a further protective mechanism. Fasting caused changes in milk osmolality, lactose, sodium and potassium concentrations indicative of a marked disturbance of milk synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)     

Exaggerated responsiveness of immunoreactive atrial natriuretic peptide to saline infusion in chronic renal failure

Plasma levels of immunoreactive alpha human atrial natriuretic peptide (IR-ANP) were measured in nine patients with chronic renal failure before and after removal of 1.3-3.7 litres of fluid by ultrafiltration and again during volume repletion with intravenous sodium chloride solution (150 mmol/l: saline). Baseline levels of IR-ANP were elevated but fell by 22% during ultrafiltration. Saline infusion induced a rapid and steep rise in IR-ANP levels which were 150% of baseline while body weight was still 2% below baseline. Changes in plasma renin, angiotensin II, aldosterone and vasopressin during the study were slight compared with the change in IR-ANP, but noradrenaline levels rose threefold during ultrafiltration. There was a significant positive relationship between arterial pressure and IR-ANP levels before and after ultrafiltration. These results lend support to the suggestion that atrial peptides are of physiological importance, especially in states of chronic fluid overload such as chronic renal failure.     

Effect of potassium supplementation on renal tubular function,ambulatory blood pressure and pulse wave velocity in healthy humans

Abstract

Background. Potassium is the main intracellular cation, which contributes to keeping the intracellular membrane potential slightly negative and elicits contraction of smooth, skeletal and cardiac muscle. A change in potassium intake modifies both cardiovascular and renal tubular function. The purpose of the trial was to investigate the effect of dietary potassium supplementation, 100 mmol daily in a randomized, placebo-controlled, crossover trial of healthy participants during two periods of 28 days duration. The participants (N = 21) received a diet that was standardized regarding energy requirement, and sodium and water intake. Methods. 24-hour ambulatory blood pressure (ABP) and applanation tonometry were used to assess blood pressure, pulse wave velocity (PWV), augmentation index (AIx) and central blood pressure (CBP). Immunoassays were used for measurements of plasma concentrations of vasoactive hormones: renin (PRC), angiotensin II (Ang II), aldosterone (Aldo), atrial natriuretic peptide (ANP), vasopressin (AVP), pro-brain natriuretic peptide (pro-BNP),endothelin (Endo), urinary excretions of aquaporin 2 (AQP2), cyclic AMP (cAMP), and the β-fraction of the epithelial sodium channel (ENaC_ß). Results. AQP2 excretion increased during potassium supplementation, and free water clearance fell. The changes in urinary potassium excretion and urinary AQP2 excretion were significantly and positively correlated. Aldo increased. GFR, u-ENaC- β, PRC, Ang II, ANP, BNP, Endo, blood pressure and AI were not significantly changed by potassium supplementation, whereas PWV increased slightly. Conclusions. Potassium supplementation changed renal tubular function and increased water absorption in the distal part of the nephron. In spite of an increase in aldosterone in plasma, blood pressure remained unchanged after potassium supplementation.

ClinicalTrials.Gov Identifier: NCT00801034     

Effect of posture on plasma immunoreactive atrial natriuretic peptide concentrations in man

The effect of changes of posture on plasma atrial natriuretic peptide concentrations and renal function was studied in normal human volunteers. Plasma atrial natriuretic peptide concentrations increased in the supine posture, reached a maximum value after 30-60 min, remained elevated for 4 h and decreased to baseline values on return to the upright posture. Inflation of antishock trousers, which apply positive pressure to the legs and lower abdomen, attenuated the fall in plasma atrial natriuretic peptide concentration in the upright position. In the supine posture there were increases in urine flow rate, sodium, lithium, fractional sodium and fractional lithium clearances. Fractional distal water and sodium excretion, and total distal water and sodium reabsorption, which were estimated by the lithium clearance technique, also increased. Heart rate and systolic and diastolic blood pressures decreased in the supine and increased on return to the upright posture. Inflation of antishock trousers prevented the increase in heart rate in the upright posture. The contribution of haemodynamic factors to the increase in plasma atrial natriuretic peptide concentrations in the supine position and the relationship between this increase and the associated changes in renal function are discussed. However, the contribution of atrial natriuretic peptide to these changes is uncertain.     

Effect of carbamazepine on plasma and urine arginine-vasopressin

1. Five normal subjects were studied before and during treatment with carbamazepine. 2. Plasma sodium, plasma and urine arginine-vasopressin and urine osmolality were measured during a day of water deprivation, before and during drug treatment. 3. During treatment with carbamazepine plasma sodium increased wheras plasma and urine arginine-vasopressin and urine osmolality decreased. Plasma and urine arginine-vasopressin were signifi"antly correlated with urine osmolality. However, carbamazepine did not affect the osmolality of urine produced by the kidney, in response to endogenous arginine-vasopressin. 4. Plasma and urine arginine-vasopressin were significantly correlated with plasma sodium on both control and drug-treatment days, but the relationships of plasma and urine arginine-vasopressin to plasma sodium were different during carbamazepine treatment, as compared with the control period. 5. It is suggested that the threshold of the hypothalamic osmoreceptors for release of arginine-vasopressin is modified by carbamazepine, and that this may be either a direct action or secondary to another action of the drug.