Prenatal exposure to ethanol causes partial diabetes insipidus in adult rats

Chronic consumption of ethanol in adult rats and humans leads to reduced AVP-producing neurons, and prenatal ethanol (PE) exposure has been reported to cause changes in the morphology of AVP-producing cells in the suprachiasmatic nucleus of young rats. The present studies further characterize the effects of PE exposure on AVP in the young adult rat, its hypothalamic synthesis, pituitary storage, and osmotically stimulated release. Pregnant rats were fed a liquid diet with 35% of the calories from ethanol or a control liquid diet for days 7-22 of pregnancy. Water consumption and urine excretion rate were measured in the offspring at 60-68 days of age. Subsequently, the offspring were infused with 5% NaCl at 0.05 ml.kg(-1).min(-1) with plasma samples taken before and at three 40-min intervals during infusion for measurement of AVP and osmolality. Urine output and water intake were approximately 20% greater in PE-exposed rats than in rats with no PE exposure, and female rats had a greater water intake than males. The relationship between plasma osmolality and AVP in PE-exposed rats was parallel to, but shifted to the right of, the control rats, indicating an increase in osmotic threshold for AVP release. Pituitary AVP was reduced by 13% and hypothalamic AVP mRNA content was reduced by 35% in PE-exposed rats. Our data suggest that PE exposure can cause a permanent condition of a mild partial central diabetes insipidus.     

Effects of prenatal ethanol exposure and sex on the arginine vasopressin response to hemorrhage in the rat

AVP synthesis, storage, and osmotically stimulated release are reduced in young adult rats exposed prenatally to ethanol (PE). Whether the reduced release of AVP to the osmotic stimulus is due to impairment of the vasopressin system or specifically to an osmoreceptor-mediated release is not known. The present experiments were done, therefore, to determine whether a hemorrhage-induced AVP response would also be diminished in PE-exposed rats. Pregnant rats were fed either a control liquid diet [no prenatal ethanol (NPE)] or a liquid diet with 35% of the calories from ethanol from days 7-21 of pregnancy. Offspring were weaned at 3 wk of life. At 11 wk of age, femoral arterial catheters were surgically placed, and blood volumes were determined at 12 wk. Three days later, two hemorrhages of 10% of the blood volume were performed with samples taken before and 10 min after the hemorrhages. After a 20% blood loss, plasma AVP was 19% higher in NPE rats than in the PE rats despite no differences in mean arterial blood pressure (MABP). Also, hypothalamic AVP mRNA and pituitary AVP content were reduced in PE rats. Furthermore, confirming an earlier report of sex differences in AVP release, the hemorrhage-induced hormone response was twofold greater in female rats than male rats, regardless of previous ethanol exposure. These studies demonstrate that the AVP response to hemorrhage is reduced in PE rats independently of differences in MABP. The data are compatible with a theory of a reduced number of hemorrhage-responsive vasopressinergic neurons capable of stimulated AVP release in PE rats.     

Effects of time of day, gender, and menstrual cycle phase on the human response to a water load

Estrogen and progesterone interference with renal actions of arginine vasopressin (AVP) has been shown. Thus we hypothesized that women will have a higher water turnover than men and that the greatest difference will be during the luteal phase of the menstrual cycle. Seven men (32 +/- 3 yr) and six women (33 +/- 2 yr) drank 12 ml water/kg lean body mass on different days at 0800 and at 2000 following 10 h of fast and a standardized meal at 0600 and 1800. Women participated on days 4-11 and 19-25 of the menstrual cycle. Initial urine and plasma osmolalities and urine flow rates were similar in all experiments. The cumulative urine voided over 3 h following the morning drink was less in men (73 +/- 12% of the water load) compared with women in either the follicular (100 +/- 3%) or luteal phases (102 +/- 10%) of the menstrual cycle. Nighttime values (30-43% of the water load) were lower in all experiments and were not different between sexes or menstrual cycle phases. Plasma AVP was higher at night and may contribute to this diurnal response. The data are generally consistent with the stated hypothesis; however, possibly owing to the greatly reduced urine flow in both sexes at night, a difference between sexes was not observed at that time.     

Fluid conservation in athletes: responses to water intake, supine posture, and immersion

The roles of antidiuretic hormone (ADH) and aldosterone in the elicited diuretic responses of trained and untrained men to seated, supine, and head-out water immersed conditions were studied. Volunteers were comprised of groups of six untrained individuals, six trained swimmers, and six trained runners. Each subject underwent three protocols, six hours in a seated position, supine position, or immersion (35 degrees C water). The last two protocols were preceded and followed by 1 h of seated position. After 10 h of fasting, 0.5% body wt of water was drunk. One hour later the trained groups had higher urine osmolalities (P less than 0.05) and urinary excretion rates of ADH (P less than 0.05) and lower urine flow rates (P less than 0.05) than untrained subjects. Throughout the sitting protocol, urinary ADH was also higher in both trained groups (P less than 0.05). Both supine posture and immersion resulted in significant decreases in urinary ADH in the untrained subjects (P less than 0.05) but no changes wer noted in swimmers and only during the second hour of immersion in the runners (P less than 0.05). The natriuresis and kaliuresis were greater during immersion than in the supine position but plasma renin activity, measured only in trained groups, and plasma aldosterone, measured in the untrained group, were decreased similarly with both protocols. The increases in urinary sodium excretion and urine flow rate were lower in trained than untrained subjects during the supine and immersion protocols (P less than 0.05). The data are compatible with an increased osmotic but decreased volume sensitivity of ADH control in trained men.     

Cardiorenal-endocrine responses to head-out immersion at night

Cardiorenal-endocrine responses to 3-h head-out immersion (HOI) (water temperature = 34.5 +/- 0.5 degrees C) were studied during day (0900-1400 h) and night (2300-0400 h) in six hydropenic male human subjects. Although HOI induced a reversible increase in urine flow in all subjects, the response was faster and greater in magnitude during the day compared with night (P less than 0.05). Na excretion and osmolal clearance (Cosm) also followed the identical response pattern as urine flow, and in fact, the HOI-induced diuresis was entirely accounted for by the increased Cosm. Endogenous creatinine clearance was not different between the day and the night and remained unchanged during HOI. Both plasma renin activity and aldosterone concentration and urinary aldosterone excretion were nearly twofold greater during the day compared with night before HOI but decreased to the same level during HOI in both daytime and the nighttime series (P less than 0.05). There was no correlation between the Na excretion rate and renin-aldosterone levels either before or during HOI. Plasma antidiuretic hormone (ADH) level was comparable between day and night before HOI and decreased to a similar level during HOI in both daytime and nighttime series (P less than 0.05 for nighttime HOI). Cardiac output increased from 3.3 1/min before HOI to 5-6 1/min during HOI without showing any significant circadian difference. Hematocrit, hemoglobin, and plasma concentrations remained unchanged under all conditions. It is concluded that the renal response to HOI is subject to nocturnal inhibition, which cannot be attributed to circadian differences in the degree of HOI-induced central blood pooling, renin-aldosterone, or ADH responses.     

Atrial natriuretic factor inhibits vasopressin secretion in conscious sheep

To test the hypothesis that atrial natriuretic factor (ANF) has a centrally mediated action on body fluid homeostasis, the effects of intracerebroventricularly (ICV) infused ANF on plasma vasopressin (AVP) concentration and urinary water and electrolyte excretion were investigated in euhydrated and water-deprived conscious sheep. ICV ANF decreased plasma AVP concentration and increased urinary free water excretion in euhydrated sheep, with excretion of Na and K unaltered. However, ICV ANF did not affect urinary volume, free water clearance, or excretion of Na and K in dehydrated animals, although plasma AVP concentration was significantly decreased. The relationship between urine volume and plasma AVP concentration was fitted by a power curve: urine volume = 0.79 X [AVP]-0.71; urine volume changes very little as a function of AVP concentration at the higher ranges. Intravenous infusion of the same amount of ANF was without effect on plasma AVP concentration or urinary excretion in both euhydrated and dehydrated animals. Mean arterial pressure was unchanged throughout all experiments. These results are consistent with the hypothesis that central ANF inhibits AVP secretion.     

Exaggerated ANF response to exercise in middle-aged vs. young runners

Hormonal, electrolyte, and renal responses were measured before, during, and after a marathon (42.2 km) in 14 runners: 8 young (Y) (mean age 27.8 yr) and 6 middle aged (MA) (mean aged 46.7 yr). No differences between groups in prerun values for heart rate (HR), plasma osmolality (OSM), antidiuretic hormone (ADH), aldosterone (ALDO), atrial natriuretic factor (ANF), or plasma renin activity (PRA) were found. Renal and urinary measurements were also similar between groups before the marathon. After 10 km of running, both groups had significant increases in HR, ALDO, ANF, and PRA, while OSM, Na+, and ADH remained unchanged from prerun values. The increase in plasma ANF concentrations at this point was significantly greater in the MA subjects compared with the Y (mean increase 104.1 vs. 42.8 pg/ml, respectively; P less than 0.01). Immediate postmarathon values for OSM, ADH, and Na+ were significantly higher than initial values in both groups, while HR, PRA, and ALDO continued to increase above the elevated levels found at 10 km. ANF values immediately postmarathon remained higher than prerun concentrations but were significantly reduced from those obtained at 10 km. In contrast, HR continued to rise until the completion of the run. These data are consistent with recent reports of an exaggerated ANF response in older subjects in response to central blood volume expansion.     

Plasma renin activity, vasopressin concentration, and urinary excretory responses to exercise in men

Plasma vasopressin concentration (PAVP), renal function, and effectors of vasopressin release were evaluated in male volunteers during running at heart rates of 0, 35, 70, and 100% of maximum after 10 h abstinence from water (normal hydration) and at 100% after ingestion of 300 ml water. Plasma renin activity (PRA) and PAVP were linearly correlated and correlated to work intensity over all observations. Changes in PAVP were not correlated with changes in plasma osmolality (POSMOL) and plasma volume (PV) over all observations. Furthermore, despite similar changes in POSMOL, PV, PRA, body weight, mean arterial pressure, and plasma lactate concentration, the increase in PAVP after maximal exercise was greater during normal hydration than the water-supplemented state. Decreased urine flow observed in association with exercise was characterized by increased free water and decreased osmotic and creatinine clearances. Thus increased PAVP associated with exercise appears not to play a role in the concomitant antidiuresis. Vasopressin stimuli are probably variable at different times during exercise and may include factors other than those measured.