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.

We have previously shown that ACTH administration (1 mg/day) for 5 days raises systolic blood pressure (BP) by some 20 mmHg in both normotensive and hypertensive subjects, accompanied by hypokalaemia, urinary Na retention, a rise in fasting blood glucose and a fall in plasma renin concentration (PRC). In the present study cortisol and deoxycorticosterone (DOC) were infused for 5 days in 7 and 6 subjects respectively at rates appropriate for conditions of ACTH stimulation to determine whether the effects of ACTH could be reproduced by either steroid. Cortisol infusion increased systolic BP from a control of 108 +/- 7 mmHg to 129 +/- 7 mmHg on day 5, p less than 0.001. Plasma [Na] increased from 137 +/- 1 to 139 +/- 1 mmol/l (p less than 0.01), plasma [K] fell from 3.8 +/- 0.1 to 3.6 +/- 0.1 mmol/l (p less than 0.05); blood glucose rose from 3.9 +/- 0.2 to 4.7 +/- 0.2 mmol/l (p less than 0.001); PRC fell from 26 +/- 7 to 12 +/- 3 mu iu /ml (p less than 0.05); renin substrate rose from 1629 +/- 140 to 2206 +/- 453 pmol AI/ml, (p less than 0.05); urine Na excretion fell from 93 +/- 19 to 41 +/- 10 mmol on day 2 (p less than 0.05) and rose to 209 +/- 31 mmol 48 hrs after infusion (p less than 0.001); urine output rose from 2.0 +/- 0.35 to 2.89 +/- 0.46 L on day 5, (p less than 0.01). Plasma cortisol levels were similar to those seen with ACTH treatment. DOC infusion was associated with a fall in diastolic BP (control 64.2 +/- 4.0 mmHg, day 5 57.0 +/- 4.2 mmHg, p less than 0.01). Urine Na excretion fell from 77 +/- 12 mmol/day to 49 +/- 8 mmol/day on day 1, (p = 0.06) and body weight rose from 76.0 +/- 5.8 kg to 76.8 +/- 5.9 kg day 5 (p less than 0.001). Thus in man, cortisol infusion (in contrast to DOC) at rates appropriate for conditions of ACTH stimulation reproduces both the BP and metabolic effects of ACTH. Whether cortisol acts to raise blood pressure by a classical glucocorticoid mechanism or by a hypertensinogenic mechanism is not known.

1. The haemodynamic and volume response to ACTH administration was investigated in six patients with mild, untreated essential hypertension and two patients with Addison's disease on maintenance steroids. Blood pressure, heart rate and weight were recorded daily. Plasma volume (125I-HSA) and cardiac output (thermo-dilution) were measured during the control period and on the 5th day of ACTH treatment. 2. In the hypertensive subjects, mean arterial pressure rose from 94.3 +/- 2.2 to 105.7 +/- 2.8 mmHg on the 5th day of ACTH administration (P less than 0.02). Plasma volume rose from 29.8 +/- 2.2 to 34 +/- 2.2 ml/kg. Cardiac index increased from 2.85 +/- 0.21 to 3.32 +/- 0.14 l/min per m2 (P less than 0.05). Cardiac output rose from 5.81 +/- 0.69 to 6.72 +/- 0.59 l/min. Calculated total peripheral resistance, heart rate and body weight were unchanged. No such changes were seen in patients with Addison's disease. 3. The haemodynamic characteristics of ACTH in patients with mild untreated essential hypertension are similar to those in the experimental model of ACTH induced hypertension in sheep.

ACTH 1 mg/day for 5 days raises systolic blood pressure (SBP) in normotensive and hypertensive subjects on a fixed electrolyte intake of 100 mmol/day sodium (Na) and potassium (K) (Whitworth et al. 1983). The present study examined the effect of Na intake in the high normal range on the haemodynamic and metabolic responses to ACTH. ACTH administration on a 200-300 mmol Na intake increased SBP by 35 mmHg (s.e.m. = 11, n = 5) compared with the 22 mmHg (s.e.m. = 4, n = 12) rise seen on a 100 mmol Na intake in our previous study. These studies suggest that the effects of adrenocortical steroids on blood pressure in man may be magnified by increasing dietary Na intake.