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A highly specific radioimmunoassay for arginine-vasopressin (AVP) in human urine has been developed, with a detection limit of 2.2 fmol/ml. The mean recovery of added AVP was 99.5 +/- 3.1 (S.D.)% when correction was made for the fact that an inverse relationship was observed between the recovery of AVP and the osmolality of the urine. The intra- and interassay coefficients of variation were 3.5--7 and 2.5--10% respectively. Arginine-vasopressin remains stable in urine after repeated freezing and thawing after storage at 4 or 20 degrees C for up to 7 days and at -20 degrees C for more than 3 months. During unrestricted fluid intake in normal people, the mean rate of renal excretion of AVP was 95 +/- 68 (S.D.) fmol/min. An isosmotic reduction of 9% in the plasma volume increased the excretion of AVP to 259 +/- 147 (S.D.) fmol/min. At the height of water-induced diuresis the rate of excretion fell to 70 +/- 28 (S.D.) fmol/min. Fluid deprivation for 18 h produced a moderate but significant increase in mean excretion of AVP, to a value of 116 +/- 67 (S.D.) fmol/min. Patients with compulsive water drinking showed a normal relationship between urine osmolality and the rate of excretion of AVP. In pituitary diabetes insipidus, AVP was undetectable, whereas in hereditary nephrogenic diabetes insipidus a progressive increase in the rate of excretion of AVP was observed in response to dehydration. There was a wide variation in the rate of excretion of AVP (range 126--8704 fmol/min) in patients with unexplained hyponatraemia, presumed to be due to an inappropriate secretion of antidiuretic hormone. Despite this variation, the relationship between urine osmolality and the rate of excretion of AVP clearly differed from that observed in normal people.

A method has been developed which allows estimation of the kinetic parameters of the plasma renin-angiotensinogen reaction from data obtained by autologous renin assays at several plasma dilutions. The quantitative aspects of the renin-angiotensin system were examined in 28 plasma samples from 23 healthy, normotensive pregnant women. They were compared with 20 women who were not pregnant, of whom 12 were taking oral contraceptives and eight were not. In the first 3 months of pregnancy, there was a sharp increase in plasma renin activity and concentration. Plasma angiotensinogen rose steadily throughout pregnancy. The higher concentrations of renin and angiotensinogen would lead to an increase in angiotensin formation with potentially adverse consequences. However, this increase may be reduced by the fall in the affinity between renin and angiotensinogen which is suggested by the present observation that the Michaelis-Menten constant (Km) attained values five to six times higher than those seen in women not taking oral contraceptives. The smaller increases in plasma renin and angiotensinogen induced by oral contraceptives were less effectively compensated by lower affinity. Circumstantial evidence is provided which suggests that the observed high Km values may be due to oestrogen/pregnancy-induced synthesis of an angiotensinogen with a lower affinity for renin.

Measurements have been made of hormonal changes relevant to salt and water balance during prolonged exposure to hypoxia to improve our understanding of the syndrome of acute mountain sickness. We have attempted to delineate the detailed inter-relationships between the renin-aldosterone and the vasopressin systems by a metabolically controlled study, involving an orthostatic stress (45 degrees head-up tilt) and an injection of a standard dose of ACTH to test adrenal responsiveness. Three Caucasian medical students underwent a 7-day equilibration at 150 m (Lima, Peru), followed by a 6-day sojourn at 4350 m (Cerro de Pasco, Peru) and a final 7 days at 150 m. Measurements were made of sodium and potassium balance, body weight and the 24-h renal excretion of vasopressin, cortisol and aldosterone 18-glucuronide. These variables showed little change, except for that of aldosterone 18-glucuronide, which fell sharply at altitude and rebounded even more sharply on return to sea level. At altitude, basal plasma levels of renin activity and aldosterone fell, and the response to orthostasis was attenuated, but the fall of plasma renin activity, as compared to plasma aldosterone, was delayed; on return to sea level this dissociation was exacerbated with the return of normal renin responsiveness lagging behind that of aldosterone. We suggest that unknown factors which dissociate the orthodox renin-aldosterone relationship, other than the activity of the angiotensin I-converting enzyme, are operative on exposure to hypoxia.