To determine whether responses to dehydration are altered with age, we investigated the thirst, fluid and electrolyte responses, and hormonal responses to 24 hours of water deprivation in seven healthy active elderly men (67 to 75 years old) and seven healthy young men (20 to 31 years old) who were matched for weight loss during water deprivation. After water deprivation, the older men had greater increases in plasma osmolality, sodium concentration, and vasopressin levels. However, their urinary osmolality was lower and they were less thirsty and drank less after water deprivation, so that their plasma and urine were not diluted to predeprivation levels. Regression analysis indicated increased sensitivity of vasopressin osmoreceptors in the older group, although this difference was not statistically significant. We conclude that after 24 hours of water deprivation, there is a deficit in thirst and water intake in healthy elderly men, as compared with younger men, although vasopressin osmoreceptor responsiveness is maintained or even increased. Our findings also suggest that the well-known deficit in urinary concentrating ability that occurs with age reflects renal causes and not a lack of circulating vasopressin.

SUMMARY1. The present study investigates the nature and magnitude of the renal response to plasma levels of oxytocin which might be induced by salt loading.2. Increased plasma osmolality induced by loading with NaCl is an effective stimulus for oxytocin release in the unanaesthetized male rat. Plasma oxytocin concentration was positively correlated (r = 0.77) with plasma osmolality. Plasma oxytocin (,uu./ml.) = 0 37 x (plasma osmolality (m-osmole/kg) -297).3. In anaesthetized Long Evans rats intra-atrial administration of oxytocin at rates of 0*05 and 0.15 m-u./ml. produced plasma hormone concentrations (5 + 1 and 16 + 2 ,uu./ml. respectively) within the range induced by salt loading. 6. Plasma ocytocin levels similar to those induced by severe dehydration or salt loading are effective in increasing renal Na+ and Cl-excretion and urine flow. These effects on water and electrolyte excretion appear to be independent of each other and both may be modified by the presence or absence of vasopressin.7. This study provides no evidence for a major role for oxytocin in the day to day regulation of salt or water balance under conditions of normal hydration in the male rat.

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SUMMARY1. Recordings were made from a total of 35 antidromically identified neurones in the paraventricular (PV) and supraoptic (SO) nuclei of urethane-anaesthetized lactating rats. During recording plasma osmotic pressure was raised by 12 m-osmole/ kg by injection of hypertonic solutions of NaCl, LiCl, or mannitol.2. Nine PV neurones (mean firing rate 4-2 + 1-0 (S.E.) spikes/sec) were classified as oxytocin cells because they gave a burst of activity before reflex milk-ejections. None of these showed a bursting (phasic) firing pattern. Ten PV neurones (mean firing rate 1-8 + 0-2 spikes/sec) fired phasically either before or after injection of hypertonic NaCl and were classified as vasopressin cells. The remaining six PV cells (mean firing rate 1-6 + 0-9 spikes/sec) showed no bursts of firing related to milk ejection and did not fire phasically.3. Increasing plasma osmotic pressure by injection of hypertonic NaCl increased the mean firing rate of PV oxytocin cells to 7-0 + 1-0 spikes/sec. Vasopressin cells in the PV nucleus were much less responsive and the mean firing rate after injection was 2-9 + 0-4 spikes/sec. The third group of PV neurones was unresponsive.4. Plasma oxytocin concentration (determined by radioimmunoassay) increased from 2-1 + 0-3 4au./ml. in the control period to 10-9 + 2-8 Atu./ml. 30 min after i.P.injection of 1 ml. 1-5 m-NaCl and to 14-8 + 2-8 1tu./ml. following injection of a second 1 ml. 1-5 M-NaCl. 5. The responses of oxytocin and vasopressin neurones in the SO nucleus to an increase in plasma osmotic pressure following injections of hypertonic solutions of LiCl or mannitol were similar to those observed when plasma osmotic pressure was raised by NaCl.6. It may be concluded that both oxytocin and vasopressin cells in the neurohypophysical system are responsive to the osmotic pressure of the blood plasma rather than to Na+ or Cl-concentration, that osmotic activation of oxytocin cells releases sufficient oxytocin to increase its plasma concentration, and that there may be a functional difference between the SO and PV nuclei.

Despite the common use of MDMA (ecstasy) in the UK, the mechanism underlying associated potentially fatal cerebral oedema is unclear. We used a new experimental approach working directly with clubbers to perform a study on 30 (17 male) experienced clubbers (mean 6.6 years of clubbing). Pre- and post-clubbing measurements were performed to compare plasma levels of pituitary hormones (vasopressin, oxytocin), plasma and urine osmolality, urinary pH, and plasma sodium and urea. Ecstasy consumption was confirmed by using urinary drug screening pre- and post-clubbing. MDMA was detected in the urine samples of 17 subjects, three of which tested positive during pre-clubbing tests. Mean plasma vasopressin concentration increased in the MDMA group (1.28 +/- 0.29 to 1.43 +/- 0.41 pmol/l), but fell in other participants (1.23 +/- 0.42 to 1.16 +/- 0.0.34 pmol/l). Similarly, mean plasma oxytocin concentrations increased after ingestion of MDMA (2.02 +/- 0.29 to 2.43 +/- 0.24 pmol/l), but fell in the group that did not use MDMA (2.17 +/- 0.36 pmol/l to 1.89 +/- 0.37 pmol/l). There was a significant group by time interaction for plasma osmolality and plasma sodium (p = 0.001 and p = 0.003, respectively) and between change in urinary osmolality (p < 0.001) and MDMA use, with the pattern of change being consistent with the induction of inappropriate vasopressin secretion (also known as SIADH) by MDMA. This report demonstrates SIADH in ecstasy-using "clubbers", which has important clinical implications.

Both vasopressin and PGF2 alpha are effective uterine stimulants in the non-pregnant human uterus, especially around the onset of menstruation. In order to clarify the relationship of these hormones to menstrual pain, plasma concentrations of vasopressin and two prostaglandin metabolites (15-keto-13,14-dihydro-PGF2 alpha and 11-ketotetranor PGF metabolites) were measured in serial blood samples taken premenstrually and during menstruation. Five women with premenstrual pain gave 7-9 blood samples at intervals of 30 minutes on the day preceding the onset of menstruation. From 5 women with severe primary dysmenorrhea a corresponding series of blood samples were taken during the first day of menstruation. Two groups of 5 women with no symptoms served as controls, either premenstrually or during menstruation. In the women with premenstrual pain the vasopressin concentrations were significantly higher than in the corresponding control group. Even higher and markedly fluctuating vasopressin levels were found in the women with dysmenorrhea who, in general, had more intense pain than the women with premenstrual symptoms. In the group with dysmenorrhea there was also a significant rise in plasma concentration of the PG metabolites. No such increase was seen in the group with premenstrual pain. It is concluded that the pathophysiology of premenstrual pain could imply increased vasopressin secretion. The more severe pain in primary dysmenorrhea seems to be the result of a combined effect of vasopressin and PGF2 alpha.

SUMMARY A method is described for the extraction and concentration of oxytocin from plasma which is simpler and more rapid than other available procedures. It has proved satisfactory for both radioimmunoassay and bioassay of circulating oxytocin. The recovery of added oxytocin was 60 ± 5·5% and showed no significant variation between plasma from pregnant and non-pregnant women, or plasma from other species. The sensitivity of the assay is related to the volume of plasma extracted. With a 10 ml plasma sample and the radioimmunoassay method described previously, the maximum sensitivity under optimal conditions is 0·75 μu. (1·5pg)/ml. In the second stage of human labour, oxytocin is not detectable in maternal plasma at this level of sensitivity. Of 36 cord venous plasma samples studied, 15 showed positive results in the range 1·5–20 μu. (3–40 pg)/ml; of 16 simultaneous cord arterial and venous plasmas, 12 showed positive results; the arterial samples showed a range of 8–145 μu. (7–290 pg)/ml with an average of 45 μu./ml; the venous samples showed a range of 0–100 μu. (0–200 pg)/ml with an average of 24 μu./ml. Plasma oxytocin levels during the second stage of labour in the goat averaged 120 μu. (240 pg)/ml by radioimmunoassay and 100 μu. (200 pg)/ml by bioassay. The half-life of infused oxytocin in the non-pregnant human subject as determined by radioimmunoassay was 5 min.

Major changes in behavioural measures of anxiety and in stress hormones can result from the soya isoflavone content of rat diet. These changes are as striking as those seen following drug administration and could form an important source of variation between laboratories.