ACTH administration (0.5 mg Synacthen Depot I/M 12 hourly for 5 days) significantly increased systolic blood pressure in normotensive subjects (n=6) and mild essential hypertensives (n=6) but not in 2 Addisonian women, indicating that the pressure rise was adrenally dependent. ACTH administration was associated with urinary sodium retention, hypokalaemia, elevation of fasting blood glucose, lymphopaenia and eosinopaenia. Body weight was increased only in the normotensive subjects. Plasma renin concentration fell and renin substrate rose. Inactive renin fell in the hypertensive subjects only. Plasma cortisol, 11-deoxycortisol, corticosterone, deoxycorticosterone, 17 alpha-hydroxyprogesterone and 17-hydroxy, 20-dihydroprogesterone were all increased by ACTH treatment. Plasma aldosterone rose initially in the normotensives but then fell. ACTH administration in man produces metabolic and hormonal changes similar to those produced by ACTH in sheep but the rise in blood pressure is systolic only in man. The steroid(s) responsible for the blood pressure rise with ACTH in man have not been defined.

The blood pressure and metabolic effects of 9 alpha-fluorocortisol at 0.15 mg/day and 1.5 mg/day were examined in man. At high dose, systolic pressure and body weight rose, and plasma [K+], urinary sodium excretion and renin concentration fell. At low dose similar metabolic effects were seen but blood pressure was unchanged. 9 alpha-Fluorocortisol has 'mineralocorticoid' effects in man at a dose which does not alter blood pressure. These studies do not provide evidence of a 'hypertensinogenic' class of steroid hormone action in man.

The present study examined the effects of low dose ACTH administration (0.1 mg/day for 2 days) on plasma renin concentration, (PRC), activity (PRA) and substrate (PRS), cortisol and aldosterone in man. Six healthy male volunteers on a diet calculated to contain 150 mmol Na/day received an infusion of 5% dextrose (6 ml/h) for 24 hours, then ACTH (Synacthen, Ciba-Geigy) was added to the infusion at the rate of 100 micrograms per day, for 48 h. Blood samples were taken four hourly for determination of plasma cortisol, aldosterone, PRC, PRA and PRS. There was a highly significant increase in plasma cortisol and aldosterone concentrations during ACTH infusion compared with dextrose infusion, but no significant increase in active or inactive PRC, PRA or PRS. In a separate study of 15 healthy male volunteers, dexamethasone (1 mg at 2300 h) suppressed plasma cortisol but had no effect on PRC. These results do not support the view that stimulation of aldosterone by ACTH is mediated through the renin angiotensin system.

Active (A) and inactive (I) plasma renin concentrations (PRC) were examined during haemodialysis in relation to blood pressure and body weight changes. Patients had either one (n = 15) or two (n = 51) remnant kidneys in situ, or were anephric (n = 4). 6 of the two remnant kidney patients had non-functioning renal allografts. Inactive renin was activated by acidification. Renin assay was by enzyme kinetic technique using sheep substrate and angiotensin I radioimmunoassay. Cryoactivation during handling was excluded. For the whole patient group the proportion of IPRC was inversely related to APRC in pre-dialysis plasma (p < 0.001). APRC and IPRC did not change with heparinisation nor did activation of renin occur across the dialyser. Dialysis with up to 3 kg reduction in body weight did not consistently raise APRC or IPRC. Blood pressure was not significantly correlated with IPRC or APRC during dialysis. In all situations a high APRC was associated with a low IPRC: APRC ratio consistent with preferential secretion of the active form and/or consumption of the inactive renin zymogen.