The value of urine osmolality as an index of stress in the ovine fetus

In ovine fetuses, during 100-130 days of gestation, urine osmolalities less than 175 mosmol/kg water were associated with plasma immunoreactive adrenocorticotrophin (ACTH) concentrations below 40 pg/ml in 40/41 samples. In 18/29 fetuses with urine osmolalities greater than 175 mosmol/kg water plasma ACTH was significantly elevated. In 38 samples of fetal blood there was a significant correlation between plasma ADH and ACTH concentrations. By least squares regression the equation to the line was [ACTH] = 5.06 + 3.70 [ADH] (r = 0.62, P less than 0.001). In 50 samples from fetuses of gestational ages 100-140 days, with urine osmolalities of 302 +/- 86 mosmol/kg (mean +/- SD) the blood pH, pO2 and pCO2 values were not significantly different from those in 50 samples from fetuses with urine osmolalities of 125 +/- 22 mosmol/kg. It is proposed that the measurement of fetal urine osmolality provides a good index of fetal stress. A fetus with a urine osmolality less than 175 mosmol/kg is almost invariably in the optimum, unstressed condition.     

Renal resistance to vasopressin in poorly controlled type 1 diabetes mellitus

To investigate the hypothesis that diabetes induces nephrogenic diabetes insipidus, we studied the urine-concentrating ability in response to vasopressin (AVP) in 12 patients with insulin-dependent diabetes mellitus (IDDM) and 12 nondiabetic controls. Subjects were euglycemic-clamped, and after oral water loading, AVP was infused intravenously for 150 min. AVP induced a greater (P<0.001) rise in urine osmolality in controls (67.6+/-10.7 to 720+/-31.1 mosmol/kg, P<0.001) than in IDDM patients (64.3+/-21.6 to 516.7+/-89.3 mosmol/kg, P<0.001). Urinary aquaporin-2 concentrations after AVP infusion were higher in controls (611.8+/-105.6 fmol/mg creatinine) than in IDDM (462.0+/-94.9 fmol/mg creatinine, P = 0. 003). Maximum urine osmolality in IDDM was inversely related to chronic blood glucose control, as indicated by Hb A(Ic) (r = -0.87, P = 0.002). To test the hypothesis that improved glycemic control could reverse resistance to AVP, 10 IDDM subjects with poor glycemic control (Hb A(Ic) >9%) were studied before (B) and after (A) intensified glycemic control. Maximum urine osmolality in response to AVP increased with improved glycemic control (B, 443.8+/-49.0; A, 640.0+/-137.2 mosmol/kg, P<0.001), and urinary aquaporin-2 concentrations after AVP increased from 112.7 +/-69 to 375+/-280 fmol/mg creatinine (P = 0.006), with improved glycemic control. Poorly controlled IDDM is associated with reversible renal resistance to AVP.     

Attenuation of vasopressin-induced antidiuresis in poorly controlled type 2 diabetes

Renal resistance to vasopressin has been demonstrated in type 1 diabetes and in type 2 diabetes with nephropathy. However, renal response to vasopressin in type 2 diabetes without nephropathy has not been studied. We studied 10 subjects with poorly controlled type 2 diabetes (PCDS; Hb A(1c) >9%), 10 subjects with well-controlled type 2 diabetes (WCDS; Hb A(1c) <7%), and 10 matched nondiabetic control subjects (NDCS) during a euglycemic 8-h water deprivation test. None of the subjects had nephropathy. Water deprivation caused similar rises in plasma vasopressin concentrations in all three groups, but the rise in urine osmolality in PCDS (280.3 +/- 49.7 to 594.4 +/- 88.5 mosmol/kgH(2)O) was lower than in WCDS (360.7 +/- 142.8 to 794.1 +/- 77.3 mosmol/kgH(2)O, P < 0.001) or NDCS (336.0 +/- 123.3 to 786.5 +/- 63.3 mosmol/kgH(2)O, P = 0.019). Total urine output was higher in the PCDS than in WCDS and NDCS (P < 0.05). Linear regression analysis showed that, in PCDS, the osmotic thresholds for thirst (291.9 +/- 4.6 mosmol/kgH(2)O) and vasopressin release (291.1 +/- 2.9 mosmol/kgH(2)O) were higher compared with WCDS (286.6 +/- 1.8 and 286.0 +/- 3.6 mosmol/kgH(2)O, respectively) and NDCS (286.0 +/- 2.4 and 284.1 +/- 4.7 mosmol/kgH(2)O, respectively) (between groups P < 0.001 for both variables). Under conditions of euglycemia, PCDS have impaired renal response to vasopressin and elevated osmotic threshold for thirst and vasopressin release in response to dehydration. Under conditions of chronic hyperglycemia, these abnormalities may significantly contribute to the development of dehydration in PCDS.     

Effect of medium osmolality on the growth of murine continuous marrow cultures

The effect of medium osmolality was examined in primary, continuous bone-marrow cultures established from TO strain mice. The non-adherent cell population increased exponentially between weeks 2 and 5 and thereafter declined steadily. The number of CFU-GM followed a similar pattern but showed greater variability. The optimum osmolality in 4 week old cultures was found to be about 345 mosmol/kg which was higher than the plasma osmolality (n = 20; mean = 323.3 mosmol/kg; range = 313-331). Maximum non-adherent cell numbers were found at about 345 mosmol/kg (better than half-maximum between 320 and 370 mosmol/kg). CFU-GM numbers in the culture supernatant were maximal at about 355 mosmol/kg (better than half-maximum between 320 and 400 mosmol/kg). An adherent layer developed over a wider range of osmolality than supported granulopoiesis (better than half-maximum between 258 and 402 mosmol/kg). It was necessary to increase the osmolality of Fischer's medium in order to obtain maximum growth.     

Effect of Medium Osmolality On the Growth of Murine Continuous Marrow Cultures

The effect of medium osmolality was examined in primary, continuous bone-marrow cultures established from to strain mice. the non-adherent cell population increased exponentially between weeks 2 and 5 and thereafter declined steadily. the number of CFU-GM followed a similar pattern but showed greater variability. the optimum osmolality in 4 week old cultures was found to be about 345 mosmol/kg which was higher than the plasma osmolality (n= 20; mean = 323.3 mosmol/kg; range = 313–331). Maximum non-adherent cell numbers were found at about 345 mosmol/kg (better than half-maximum between 320 and 370 mosmol/kg). CFU-GM numbers in the culture supernatant were maximal at about 355 mosmol/kg (better than half-maximum between 320 and 400 mosmol/kg). an adherent layer developed over a wider range of osmolality than supported granulopoiesis (better than half-maximum between 258 and 402 mosmol/kg). It was necessary to increase the osmolality of Fischer's medium in order to obtain maximum growth.     

Role of renal prostaglandins in the fall in urine osmolality after papillary micropuncture

The effect of micropuncture of the renal papilla through an intact ureter on urinary concentrating ability of rats was examined. Micropuncture of the renal papilla caused a fall in urine osmolality in the punctured kidney from 1718 +/- 106 to 1035 +/- 79 mosmol/kg X H2O. In order to investigate the role of renal prostaglandins in this process, PGE2 excretion was measured and found to increase from 63.4 +/- 14.0 to 205.5 +/- 57.1 pg/min. Urine osmolality and PGE2 excretion from the contralateral kidney were not significantly altered. In animals given meclofenamate (2 mg/kg X hr), renal PGE2 excretion was reduced to 22.3 +/- 5.1 pg/min prior to micropuncture and it remained low at 8.9 +/- 1.8 pg/min after papillary micropuncture. Meclofenamate also blocked the fall in urine osmolality caused by micropuncture of the renal papilla, with urine osmolality averaging 1940 +/- 122 before and 1782 +/- 96 mosmol/kg X H2O after the micropuncture. These results indicated that papillary micropuncture through an intact ureter increased renal PGE2 excretion and that a rise in renal production of PGE2 or some other prostanoid is associated with a fall in urine concentrating ability.     

Effect of osmolality on the initiation of sperm motility in Xenopus laevis

1. Seminal plasma of the South African clawed toad Xenopus laevis exhibited osmolality around 250 mosmol/kg isotonic to blood plasma. 2. Spermatozoa remained immotile when the semen was diluted in solutions of 100 mM NaCl, 100 mM KCl or 200 mM glucose containing 20 mM Hepes-NaOH buffer which exhibited almost the same osmolalities (approximately 240 mosmol/kg) as seminal plasma. 3. The spermatozoa became motile in these three solutions if the osmolalities were decreased. 4. These suggest that motility of Xenopus sperm is suppressed by seminal osmolality in the reproductive organ and initiated by a decrease of osmolality when they are spawned into hypotonic fresh water.     

Stimulation of myeloid colony growth from peripheral blood by medium with an initially low osmolality

The clonal growth of myeloid colonies from peripheral blood was maximal when cultures were established with an initial osmolality of 220 mosmol/kg which increased during incubation as a result of partial drying. When osmolality was stabilized by secondary humidification, the optimum osmolality was 270 mosmol/kg, but growth was always two- to fivefold less than similar cultures established at low osmolality and incubated on an open shelf. Cultures established at 270 mosmol/kg or above were statistically similar whether or not drying was eliminated. Maximum colonies were apparent after 14 days incubation under both conditions; addition of conditioned medium did not alter the pattern of growth. The greater sensitivity of cultures established at 220 mosmol/kg is advantageous when assaying circulating progenitors in pathological conditions where a low number of granulocyte/macrophage colony-forming units is common.     

Sex differences in osmotic regulation of AVP and renal sodium handling.

To determine sex differences in osmoregulation of arginine vasopressin (AVP) and body water, we studied eight men (24 +/- 1 yr) and eight women (29 +/- 2 yr) during 3% NaCl infusion [hypertonic saline infusion (HSI); 120 min, 0.1 ml. kg body wt(-1). min(-1)]. Subjects then drank 15 ml/kg body wt over 30 min followed by 60 min of rest. Women were studied in the early follicular (F; 16.1 +/- 2.8 pg/ml plasma 17beta-estradiol and 0.6 +/- 0.1 ng/ml plasma progesterone) and midluteal (L; 80.6 +/- 11.4 pg/ml plasma 17beta-estradiol and 12.7 +/- 0.7 ng/ml plasma progesterone) menstrual phases. Basal plasma osmolality was higher in F (286 +/- 1 mosmol/kgH(2)O) and in men (289 +/- 1 mosmol/kgH(2)O) compared with L (280 +/- 1 mosmol/kgH(2)O, P < 0.05). Neither menstrual phase nor gender affected basal plasma AVP concentration (P([AVP]); 1.7 +/- 4, 1.9 +/- 0.4, and 2.2 +/- 0.5 pg/ml for F, L, and men, respectively). The plasma osmolality threshold for AVP release was lowest in L (x-intercept, 263 +/- 3 mosmol/kgH(2)O, P < 0.05) compared with F (273 +/- 2 mosmol/kgH(2)O) and men (270 +/- 4 mosmol/kgH(2)O) during HSI. Men had greater P([AVP])-plasma osmolality slopes (i.e., sensitivity) compared with F and L (slopes = 0.14 +/- 0.04, 0.09 +/- 0.01, and 0.24 +/- 0.07 for F, L, and men, respectively, P < 0.05). Despite similar Na+-regulating hormone responses, men excreted less Na+ during HSI (0.7 +/- 0.1, 0.7 +/- 0.1, and 0.5 +/- 0.1 meq/kg body wt for F, L, and men, respectively, P < 0.05). Furthermore, men had greater systolic blood pressure (119 +/- 5, 119 +/- 5, and 132 +/- 3 mmHg for F, L, and men, respectively, P < 0.05) than F and L. Our data indicate greater sensitivity in P([AVP]) response to changes in plasma osmolality as the primary difference between men and women during HSI. In men, this greater sensitivity was associated with an increase in systolic blood pressure and pulse pressure during HSI, most likely due to a shift in the pressure-natriuresis curve.     

Influence of opioid peptides on release from vasopressin and oxytocin neurones of the hypothalamoneurohypophyseal system: effects of naloxone in the conscious rat

We examined the effects of acute and chronic treatments with naloxone on release of vasopressin and oxytocin from the hypothalamoneurohypophyseal system (HNS) in conscious, chronically instrumented Long-Evans rats. Plasma concentrations of vasopressin-associated neurophysin and oxytocin-associated neurophysin were evaluated before and during an intravenous infusion of 18% saline at 100 microL.kg-1 body weight.min-1 for 60 min. Acute treatment with naloxone (2.75 mumol/kg, intravenous) did not measurably alter basal plasma osmolality or vasopressin-associated neurophysin concentration, but it caused a three-fold rise in basal plasma oxytocin-associated neurophysin concentration (16 +/- 2 to 46 +/- 3 fmol/mL, p less than 0.005). Chronic treatment with naloxone (13.75 mumol/day, subcutaneous pellets) increased plasma osmolality (292 +/- 1 to 300 +/- 2 mosmol/kg H2O, p less than 0.01) by day 5, but it had no measurable effects on basal vasopressin- or oxytocin-associated neurophysin concentration. There were also no significant differences in plasma sodium concentration (144.8 +/- 1.1 vs. 142.2 +/- 1.4 mequiv./L) under both conditions. Acute and chronic treatments with naloxone accompanied by salt loading produced a five- and four-fold decrease in the rates that plasma concentration of vasopressin-associated neurophysin changed with plasma osmolality, compared with untreated salt-loaded control rats. For oxytocin secretion from the HNS, both treatments accompanied by salt loading substantially decreased the threshold for changes in relation to plasma osmolality; the rise in plasma concentration of oxytocin-associated neurophysin was similar at all levels of hyperosmotic stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)     

Dehydration-induced vasopressin secretion in humans: involvement of the histaminergic system

In rats, the hypothalamic neurotransmitter histamine participates in regulation of vasopressin secretion and seems to be of physiological importance, because blockade of the histaminergic system reduces dehydration-induced vasopressin secretion. We investigated whether histamine is also involved in regulation of vasopressin secretion during dehydration in humans. We found that 40 h of dehydration gradually increased plasma osmolality by 10 mosmol/kg and induced a fourfold increase in vasopressin levels. Pretreatment with the H(2)-receptor antagonists cimetidine or ranitidine significantly reduced the dehydration-induced increase in vasopressin levels approximately 40% after 34 and 37 h of dehydration, whereas this was not the case with the H(1)-receptor antagonist mepyramine. Dehydration reduced aldosterone secretion by approximately 50%. This effect of dehydration was reduced by both H(1)- and H(2)-receptor blockade after 16 and/or 34 h of dehydration. We conclude that vasopressin secretion in response to dehydration in humans is under the regulatory influence of histamine and that the effect seems to be mediated via H(2)-receptors. In addition, the regulation of aldosterone secretion during dehydration also seems to involve the histaminergic system via H(1) and H(2) receptors.     

Hormonal regulation of renal sodium and water excretion during normotensive sodium loading in conscious dogs

Saline was infused intravenously for 90 min to normal, sodium-replete conscious dogs at three different rates (6, 20, and 30 micromol x kg(-1) x min(-1)) as hypertonic solutions (HyperLoad-6, HyperLoad-20, and HyperLoad-30, respectively) or as isotonic solutions (IsoLoad-6, IsoLoad-20, and IsoLoad-30, respectively). Mean arterial blood pressure did not change with any infusion of 6 or 20 micromol x kg(-1) x min(-1). During HyperLoad-6, plasma vasopressin increased by 30%, although the increase in plasma osmolality (1.0 mosmol/kg) was insignificant. During HyperLoad-20, plasma ANG II decreased from 14+/-2 to 7+/-2 pg/ml and sodium excretion increased markedly (2.3+/-0.8 to 19+/-8 micromol/min), whereas glomerular filtration rate (GFR) remained constant. IsoLoad-20 decreased plasma ANG II similarly (13+/-3 to 7+/-1 pg/ml) concomitant with an increase in GFR and a smaller increase in sodium excretion (1.9+/-1.0 to 11+/-6 micromol/min). HyperLoad-30 and IsoLoad-30 increased mean arterial blood pressure by 6-7 mm Hg and decreased plasma ANG II to approximately 6 pg/ml, whereas sodium excretion increased to approximately 60 micromol/min. The data demonstrate that, during slow sodium loading, the rate of excretion of sodium may increase 10-fold without changes in mean arterial blood pressure and GFR and suggest that the increase may be mediated by a decrease in plasma ANG II. Furthermore, the vasopressin system may respond to changes in plasma osmolality undetectable by conventional osmometry.     

Prolonged hypobaric hypoxemia attenuates vasopressin secretion and renal response to osmostimulation in men.

Effects of hypobaric hypoxemia on endocrine and renal parameters of body fluid homeostasis were investigated in eight normal men during a sojourn of 8 days at an altitude of 4,559 m. Endocrine and renal responses to an osmotic stimulus (5% hypertonic saline, 3.6 ml/kg over 1 h) were investigated at sea level and on day 6 at altitude. Several days of hypobaric hypoxemia reduced body weight (-2.1 +/- 0.4 kg), increased plasma osmolality (+5.3 +/- 1.4 mosmol/kgH(2)O), elevated blood pressure (+12 +/- 1 mmHg), reduced creatinine clearance (122 +/- 6 to 96 +/- 10 ml/min), inhibited the renin system (19.5 +/- 2.0 to 10.9 +/- 0.9 mU/l) and plasma vasopressin (1.14 +/- 0.16 to 0.38 +/- 0.06 pg/ml), and doubled circulating levels of norepinephrine (103 +/- 16 to 191 +/- 35 pg/ml) and endothelin-1 (3.0 +/- 0.2 to 6.3 +/- 0.6 pg/ml), whereas urodilatin excretion rate decreased from day 2 (all changes P < 0.05 compared with sea level). Plasma arginine vasopressin response and the antidiuretic response to hypertonic saline loading were unchanged, but the natriuretic response was attenuated. In conclusion, chronic hypobaric hypoxemia 1) elevates the set point of plasma osmolality-to-plasma vasopressin relationship, possibly because of concurrent hypertension, thereby causing hypovolemia and hyperosmolality, and 2) blunts the natriuretic response to hypertonic volume expansion, possibly because of elevated circulating levels of norepinephrine and endothelin, reduced urodilatin synthesis, or attenuated inhibition of the renin system.     

The Saltiness of the Sea Breaks DNA in Marine Invertebrates: Possible Implications for Animal Evolution

More than 97 percent of the world's water is ocean and its average osmolality of 1000 mosmol/kg is much higher than the 300 mosmol/kg found in most of the intercellular fluids of vertebrates. Many marine invertebrates are osmoconformers, meaning that the osmolality of their extracellular fluid is the same as that of seawater. We report here that marine invertebrates from diverse phyla have numerous DNA breaks in their cells while they are exposed to normal seawater containing high NaCl, but that the DNA breaks decrease or disappear when the animals are acclimated to the same water diluted to 300 mosmol/kg. We speculate that, since DNA breaks cause mutations, salinity might have important background effects on the rate and course of evolution.     

Antidiuretic function in Sheehan's syndrome.

Twenty patients with postpartum hypopituitarism underwent a dehydration test followed by the administration of synthetic arginine-vasopressin (DDAVP; desmopressin). Panhypopituitarism was confirmed by hormonal assays in the basal state and after stimulation with combined luteinising hormone releasing hormone-thyrotrophin releasing hormone-insulin. All the patients were given replacement therapy with hydrocortisone and thyroid hormones. Results were compared with those in 12 normal women. Urinary concentrating ability was diminished in the patients as compared with the controls (maximum urine osmolality 688 (SEM 23) mmol (mosmol)/kg in the patients v 967 (SEM 29) mmol/kg in the controls). Also the change in urine osmolality after administration of desmopressin was greater in the patients (+9.55 (SEM 1.98)% in the patients v 2.49 (SEM 0.96)% in the controls). Partial diabetes insipidus is apparently common in Sheehan''s syndrome. This association should be borne in mind when managing these patients, especially those in acute failure.     

Clinical phenotype of nephrogenic diabetes insipidus in females heterozygous for a vasopressin type 2 receptor mutation

Nephrogenic diabetes insipidus (NDI) usually shows an X-linked recessive mode of inheritance caused by mutations in the vasopressin type 2 receptor gene (AVPR2). In the present study, three NDI families are described in which females show clinical features resembling the phenotype in males. Maximal urine osmolality in three female patients did not exceed 200 mosmol/kg and the absence of extra-renal responses to 1-desamino-8-d-arginine vasopressin was demonstrated in two of them. All affected females and two asymptomatic female family members were shown to be heterozygous for an AVPR2 mutation. Skewed X-inactivation is the most likely explanation for the clinical manifestation of NDI in female carriers of an AVPR2 mutation. It is concluded that, in female NDI patients, the possibility of heterozygosity for an AVPR2 gene mutation has to be considered in addition to homozygosity for mutations in the aquaporin 2 gene.     

Osmolality and secretion of vasopressins during pregnancy in Meriones crassus]

Endocrine and renal parameters were measured in a desert rodent, Meriones crassus. In virgin females, the urine and plasma osmolality was 2018 +/- 136 and 325 +/- 3 mosm/kg (m +/- SEM), the level of circulating vasopressin, 162 +/- 22 pg/ml and the plasma renin activity 14.3 +/- 0.9 ng/ml per h. During pregnancy, the renin-angiotensin system was activated, and the plasma vasopressin values remained similar to those of virgin animals in spite of a lower blood plasma osmotic pressure. During this period, the regulation of the hydromineral balance was modified. These data suggest a lowering of the osmotic thresholds for vasopressin and possibly also for thirst during pregnancy in this desert rodent.     

Body temperature and seawater adaptation in farmed Atlantic salmon and rainbow trout during prolonged chilling

The core temperature of the rainbow trout Oncorhynchus mykiss (3·5 kg) dropped to 1·0° C during the first 6 h of chilling at 0·5° C, remained stable until 24 h, and dropped significantly to 0·7° C after 39 h. Blood plasma osmolality increased and muscle moisture content decreased gradually with increasing chilling time. After 39 h of chilling, the rainbow trout experienced 40 mosmol l^-1 higher blood plasma osmolality and 2·8% less muscle moisture content compared with initial values. In the Atlantic salmon Salmo salar (5·3 kg), core temperature dropped to 1·3° C and blood plasma osmolality increased significantly during the first 6 h of chilling at 0·5° C, but remained relatively stable throughout the rest of the experimental period. After 39 h of chilling, the salmon experienced 20 mosmol l^-1 higher blood plasma osmolality and 0·5% less muscle moisture content compared with initial values. In rainbow trout muscle moisture content was inversely related to blood plasma osmolality indicating reduced seawater adaptation with increasing hours of chilling. No such relationship was observed in the Atlantic salmon. Hence, changes in plasma osmolality and muscle moisture in the Atlantic salmon do not indicate osmoregulatory failure since the new levels, once established, were maintained throughout the chilling time.     

Osmotic threshold and sensitivity for vasopressin release and fos expression by hypertonic NaCl in ovine fetus

In adults, hyperosmolality stimulates central osmoreceptors, resulting in arginine vasopressin (AVP) secretion. Near-term fetal sheep have also developed mechanisms to respond to intravascular hypertonicity with stimulation of in utero AVP release. However, prior studies demonstrating fetal AVP secretion have utilized plasma tonicity changes greater than those required for adult osmotically induced AVP stimulation. We sought to examine near-term fetal plasma osmolality threshold and sensitivity for stimulation of AVP secretion and to correlate plasma hormone levels with central neuronal responsiveness. Chronically instrumented ovine fetuses (130 +/- 2 days) and maternal ewes simultaneously received either isotonic or hypertonic intravascular NaCl infusions. Maternal and fetal plasma AVP and angiotensin II (ANG II) levels were examined at progressively increasing levels of plasma hypertonicity. Intravenous hypertonic NaCl gradually elevated plasma osmolality and sodium levels. Both maternal and fetal plasma AVP increased during hypertonicity, whereas ANG II levels were not changed. Maternal AVP levels significantly increased with a 3% increase in plasma osmolality, whereas fetal plasma AVP significantly increased only at higher plasma osmolality levels (over 6%). Thus the slope of the regression of AVP vs. osmolality was greater for ewes than for fetuses (0.232 vs. 0.064), despite similar maternal and fetal plasma osmolality thresholds for AVP secretion (302 vs. 304 mosmol/kg). Hyperosmolality induced Fos immunoreactivity (FOS-ir) in the circumventricular organs of the fetal brain. FOS-ir was also demonstrated in the fetal supraoptic and paraventricular nuclei (SON and PVN), and double labeling demonstrated that AVP-containing neurons in the SON and PVN expressed Fos in response to intravenous NaCl. These results demonstrate that, in the ovine fetus at 130 days of gestation, neuroendocrine responses to cellular dehydration are functional, although they evidence a relatively reduced sensitivity for AVP secretion compared with the adult.     

Suppression of ADH during water immersion in normal man.

Since previous studies from this laboratory have demonstrated that the redistribution of blood volume and concomitant relative central hypervolemia induced by water immersion to the neck causes a profound natriuresis and a suppression of the renin-aldosterone system, it was of interest to assess whether the diuresis induced by immersion was mediated by an analogous inhibition of ADH. The effects of water immersion on renal water handling and urinary ADH excretion were assessed in 10 normal male subjects studied following 14 h of overnight dehydration on two occasions, control and immersion. The conditions of seated posture and time of day were identical. During control ADH persisted at or above prestudy values. Immersion resulted in a progressive decrease in ADH excretion from 80.1 plus or minus 7 (SEM) to 37.3 plus or minus 6.3 muU/min (P smaller than 0.025). Cessation of immersion was associated with a marked increase in ADH from 37.3 +/- 6.3 muU/min to 176.6 +/- 72.6 muU/min during the recovery hour (P smaller than 0.05). Concomitant with these changes urine osmolality decreased significantly beginning as early as the initial hour of immersion from 1044 +/- 36 to 542 +/- 66 mosmol/kg H2O during the final hour of immersion (P smaller than 0.001). Recovery was associated with a significant mean increase in Uosm of 190 +/- 40 mosmol/kg H2O over the final hour of immersion (P smaller than 0.001). The suppression of ADH occurred without concomitant changes in plasma tonicity. These studies are consistent with the suggestion that in hydrated subjects undergoing immersion suppression of ADH release contributes to the enhanced free water clearance, which has been previously documented.