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1. Saralasin (Sar1-Ala8-angiotensin II), a competitive inhibitor of angiotensin II (AII), has been infused into normal subjects and patients with essential hypertension when deprived of sodium by 5 days of a 10 mmol/day sodium diet. 2. When saralasin was given by an incremental rate of infusion starting at 0·25 µg min—1 kg—1, sodium-deprived normal subjects showed a fall in standing blood pressure with no change in lying blood pressure, sodium-deprived normal-renin hypertensive patients showed no change in lying or standing blood pressure and sodium-deprived low-renin patients showed a significant sustained rise in lying and standing blood pressure. 3. These findings suggest that: (a) standing blood pressure in sodium-deprived normal subjects is angiotensin II dependent; (b) normal-renin hypertensive patients when sodium deprived by diet alone do not appear to be angiotensin II dependent (angiotensin II is unlikely therefore to be directly maintaining their blood pressure on their normal sodium intake); (c) the rise in blood pressure seen in low-renin hypertensive patients with saralasin may be a further way of distinguishing this group of patients.

1. Propranolol, saralasin and captopril changed blood pressure in normotensive as well as hypertensive subjects. 2. The percentage change in blood pressure with these three drugs for a given plasma renin activity was similar in normotensive and hypertensive subjects. 3. This suggests that when the renin-angiotensin system is maintaining blood pressure, it maintains the blood pressure to the same extent in percentage terms in normotensive and hypertensive subjects for a given plasma renin activity. 4. Saralasin has marked agonist activity, and probably underestimates the participation of the renin—angiotensin—aldosterone system in the maintenance of blood pressure. The fall in blood pressure that occurred with captopril in normal subjects on their normal sodium intake suggests that the renin—angiotensin—aldosterone system may have an important role in the control of blood pressure in normal subjects on their normal sodium intake. If it does, our results suggest that the renin—angiotensin—aldosterone system plays no greater role in maintaining blood pressure in patients with essential hypertension than normotensive subjects for a given plasma renin activity.

1. Captopril given for 5 days caused a fall in blood pressure in normotensive subjects. The percentage fall in mean supine pressure was greatest on a low sodium diet (10 mmol/day), 19.6%, least on a high sodium diet (350 mmol/day), 11%, and in between on a normal sodium diet (120 mmol/day), 16.5%. 2. Captopril caused a marked fall in plasma aldosterone in normal subjects on all three sodium intakes. 3. Captopril caused an increase in sodium excretion on the normal (120 mmol/day) and low (10 mmol/day) sodium diet but not the high sodium diet. 4. These results suggest that the renin-angiotensin-aldosterone system is a normal mechanism for maintaining blood pressure and aldosterone secretion in normotensive man. The system may also be involved in the maintenance of sodium balance. 5. These results may lead to a better understanding of the role of the renin-angiotensin-aldosterone system in the maintenance or causation of high blood pressure in essential hypertension.

1. The effects of synthetic human and rat atrial peptides on sodium and potassium ion transport has been investigated in intact human erythrocytes. 2. The effects of these peptides have been tested on the active, sodium pump-dependent (ouabain-sensitive) and on the sodium-potassium cotransport system (bumetanide-sensitive) with 86Rb used as a tracer. 3. Human (α-ANP, 28 amino acids) or rat (atriopeptin III) atrial peptides, over a wide range of concentrations, did not influence the uptake of 86Rb in either the ouabain-sensitive or the bumetanide-sensitive transport system. 4. These results suggest that the natriuretic effect of the atrial peptides is not mediated through inhibition of the sodium pump or the loop-diuretic-sensitive Na-K cotransport.

1. The plasma's ability to stimulate guinea-pig renal glucose 6-phosphate dehydrogenase (G6PD) in vitro was measured by a cytochemical technique in 23 normotensive subjects and 19 patients with hypertension, all of whom were studied on their normal sodium intake. The ability of plasma to stimulate renal G6PD was significantly (P < 0.001) increased in the hypertensive patients (mean 195 ± 52 units/ml) compared with the normotensive subjects (mean 22.2 ± 5.8 units/ml). In all 42 individuals, there was a significant correlation between diastolic pressure and the ability of plasma to stimulate G6PD (r = 0.69 P < 0.001). 2. The ability of plasma to stimulate G6PD was greatest in the hypertensive patients with values of plasma renin activity below the normal range. In the normotensive subjects the ability of plasma to stimulate G6PD was significantly greater in the older subjects. 3. As the ability of plasma to stimulate G6PD reflects its ability to inhibit Na+,K+-dependent ATPase, these results suggest that patients with essential hypertension have an increase in a circulating inhibitor of Na+,K+-ATPase. The results support the hypothesis that a rise in a circulating sodium transport inhibitor may, in part, be responsible for the rise in blood pressure in essential hypertension, and may form the link between salt intake, abnormalities of sodium transport and a rise in blood pressure.

1. Seventy-seven patients with essential hypertension and 28 normotensive subjects were studied on their normal diet (ND), on the fifth day of a high sodium diet (HS) (350 mmol/day) and on the fifth day of a low sodium diet (LS) (10 mmol/day). 2. With an increase in sodium intake, there was no change in mean blood pressure either in the normotensive subjects (ND, 120/75 ± 2.4/1.7 mmHg—HS, 119/75 ± 2.7/1.7 mmHg) or in the hypertensive subjects (ND, 173/110 ± 2.5/1.3 mmHg—HS, 174/110 ± 2.5/1.4 mmHg). 3. On the fifth day of the low sodium diet there was no change in mean blood pressure in the normotensive subjects (ND, 120/75 ± 2.5/1.7 mmHg—LS, 116/76 ± 2.7/2.0 mmHg). In contrast, the hypertensive group on the fifth day of the low salt diet had a significant fall in supine mean blood pressure compared with those on the normal diet (ND, 173/110 ± 2.5/1.3—LS, 155/102 ± 2.2/1.3 mmHg; P < 0.001). The fall in mean blood pressure was 10.8 ± 1.1 mmHg (8.4%). 4. There was a significant correlation between the fall in blood pressure with the low sodium diet and the level of blood pressure on the normal diet (r = 0.52; P < 0.001) and a significant inverse correlation with the fall in blood pressure on the low sodium diet and the rise in plasma renin activity from the normal to low sodium diet (r = -0.36; P < 0.001). 5. Nineteen patients with mild to moderate essential hypertension were studied in a double-blind randomized crossover study of moderate dietary sodium restriction using slow sodium and placebo for 1 month each. On the fourth week of placebo (mean 24 h UNa 86 ± 9 mmol), mean supine blood pressure was 7.1 mmHg lower (6.1%), P < 0.001 compared with the fourth week of slow sodium (mean 24 h UNa 162 ± 9 mmol). 6. Moderate dietary sodium restriction over 1 month caused a fall in blood pressure in patients with essential hypertension. A more severe reduction in sodium intake for a shorter period of time lowered blood pressure in hypertensive but not normotensive subjects. Part of the mechanism of this blood pressure reduction with sodium restriction appeared to be related to the severity of the hypertension and to suppression of the renin-angiotensin system.

1. Plasma levels of immunoreactive N-terminal pro-atrial natriuretic peptide (N-terminal ANP) have been measured in 25 normal subjects, 29 patients with essential hypertension, six cardiac transplant recipients, seven patients with dialysis-independent chronic renal failure and 11 patients with haemodialysis-dependent chronic renal failure. Plasma was extracted on Sep-Pak cartridges and N-terminal ANP immunoreactivity was measured using an antibody directed against pro-ANP (1–30). 2. Plasma levels of TV-terminal ANP (means ± sem) were 235.3 ± 19.2 pg/ml in normal subjects and were significantly raised in patients with essential hypertension (363.6 ± 36.3 pg/ml), in cardiac transplant recipients (1240.0 ± 196.2 pg/ml), in patients with chronic renal failure not requiring dialysis (1636.6 ± 488.4 pg/ml) and patients with chronic renal failure on maintenance haemodialysis (10 336.1 ± 2043.7 pg/ml). 3. There were positive and significant correlations between the plasma levels of TV-terminal ANP and α-human ANP (α-hANP) with individual correlation coefficients of 0.68 within the normal subjects, 0.47 in patients with essential hypertension, 0.78 in patients with dialysis-independent chronic renal failure and 0.68 in patients with haemodialysis-dependent chronic renal failure (P < 0.05 in every case). 4. Gel filtration behaviour on Sephadex G-50 of the immunoreactive N-terminal ANP from Sep-Pak extracts of plasma from normal subjects or patients was consistent with a single peak having an elution volume corresponding to that of human pro-ANP (1–67) standard. 5. These studies demonstrate that the N-terminal pro-ANP peptide is co-secreted with α-hANP in both normal subjects and patients with cardiovascular/renal disease. The higher levels of the N-terminal ANP may reflect differences in the rate of elimination from the circulation but the exact structure and functional significance of the circulating N-terminal ANP remains to be established.

1. To study the anti-hypertensive effects of atrial natriuretic peptide (ANP), eight patients with mild to moderate essential hypertension, on no treatment, were infused with α-human ANP (102–126) (37 pmol min−1 kg−1) or placebo for 60 min and observed for a further 4 h on the fifth day of low and high sodium diets in a randomized, cross-over study. 2. Plasma ANP levels increased over 30-fold into the high pathophysiological range during ANP infusion, but had returned to control values by 60 min after the end of infusion. With ANP infusion, there was a large decrease in supine blood pressure which was similar on both the low and high sodium intakes and was maximal 20–40 min after completion of the infusion. These reductions in blood pressure were sustained for a further 4 h after the end of ANP infusion and for 3 h after plasma ANP levels had returned to control values. 3. Maximal urinary sodium excretion increased 10-fold on the low sodium diet (negative sodium balance 20 mmol) and threefold on the high sodium diet (negative sodium balance 30 mmol) during ANP infusion; however, during the 4 h after infusion, urinary sodium excretion was below placebo values. During ANP infusion, packed cell volume increased significantly on both diets but returned to control values by 4 h after the end of infusion. 4. There were no significant changes in plasma renin activity compared with placebo during or after ANP infusion. However, plasma aldosterone was significantly greater than placebo values after the end of ANP infusion on both low and high sodium diets. 5. The sustained fall in blood pressure after ANP infusion appears to be unexplained by changes in sodium balance, packed cell volume and plasma ANP levels. These findings suggest that ANP may have a prolonged action on a pressor mechanism which remains to be defined.

1. The pattern of urinary acid excretion during mannitol diuresis was studied in five normal adult subjects. 2. At peak diuresis (osmolal clearance 19·3–27·9 ml/min), the urinary pH approached 6·9 irrespective of the initial pH. 3. Total hydrogen ion excretion fell sharply during mannitol diuresis. Changes in the excretion of ammonium and titratable acid were small and variable, but in each subject bicarbonate excretion increased markedly. 4. Despite previous conflicting published results urinary acid excretion during mannitol diuresis in man resembles that in the dog and is dominated by a bicarbonate diuresis.