In this double-blind crossover study, the effects of bolus infusions of 0.9% saline (NaCl) and Hartmann's solution on serum albumin, haematocrit and serum and urinary biochemistry were compared in healthy subjects. Nine young adult male volunteers received 2-litre intravenous infusions of 0.9% saline and Hartmann's solution on separate occasions, in random order, each over 1h. Body weight, haematocrit and serum biochemistry were measured pre-infusion and at 1h intervals for 6h. Biochemical analysis was performed on pooled post-infusion urine. Blood and plasma volume expansion, estimated by dilutional effects on haematocrit and serum albumin, were greater and more sustained after saline than after Hartmann's solution ( P <0.01). At 6h, body weight measurements suggested that 56% of the infused saline was retained, in contrast with only 30% of the Hartmann's solution. Subjects voided more urine (median: 1000 compared with 450ml) of higher sodium content (median: 122 compared with 73mmol) after Hartmann's than after saline (both P = 0.049), despite the greater sodium content of the latter. The time to first micturition was less after Hartmann's than after saline (median: 70 compared with 185min; P = 0.008). There were no significant differences between the effects of the two solutions on serum sodium, potassium, urea or osmolality. After saline, all subjects developed hyperchloraemia (>105mmol/l), which was sustained for >6h, while serum chloride concentrations remained normal after Hartmann's ( P <0.001 for difference between infusions). Serum bicarbonate concentration was significantly lower after saline than after Hartmann's ( P = 0.008). Thus excretion of both water and sodium is slower after a 2-litre intravenous bolus of 0.9% saline than after Hartmann's solution, due possibly to the more physiological [Na + ]/[Cl - ] ratio in Hartmann's solution (1.18:1) than in saline (1:1) and to the hyperchloraemia caused by saline.

1. Aldosterone is suppressed by sodium loading. We studied the contribution of this decrease in plasma aldosterone to the natriuresis after acute sodium loading in healthy volunteers. 2. Two litres of saline [0.9% (w/v) NaCl] were infused during the second hour of a 6 h infusion of aldosterone (3 pmol min −1 kg −1 ) or placebo in eight healthy young men. On the placebo day, plasma aldosterone decreased by 30 min after the start of saline infusion and remained suppressed. During aldosterone infusion, plasma aldosterone was maintained at around 400 pmol/l. 3. Urinary sodium excretion, lithium clearance and plasma atrial natriuretic peptide increased and plasma renin activity decreased after saline infusion, whether or not aldosterone was infused. However, from 60 to 240 min after saline infusion, natriuresis was significantly less during aldosterone infusion than on the placebo day. In addition, saline loading led to a progressive increase in the ratio of sodium clearance to lithium clearance, used as an index of the fractional distal tubular rejection of sodium, and in the ratio of urinary sodium to potassium. These increases were prevented by the infusion of aldosterone. 4. This study suggests that there are differences in the mechanisms determining the early and the later responses to an acute sodium load. Suppression of aldosterone may explain much of the later increase in natriuresis after saline infusion. In addition, the results are consistent with a role for atrial natriuretic peptide in the immediate increase in sodium excretion after saline loading.

1. The effect of changes of dietary sodium chloride intake and posture on plasma atrial natriuretic peptide concentration and renal function was studied in 11 normal human volunteers. 2. Plasma atrial natriuretic peptide concentration was higher in the upright posture on a high than it was on a medium or low salt diet. On the medium and high but not on the low salt diet the concentration increased significantly on adoption of the supine posture. 3. Creatinine, sodium, lithium and fractional lithium clearances, fractional distal sodium excretion and total distal water and sodium reabsorption, which were estimated by the lithium clearance technique, were significantly higher on the high than on the low salt diet. The medium salt intake gave intermediate values. 4. Heart rate while upright was significantly higher on the low than on either the medium or the high salt diets. Systolic blood pressure was unaffected by salt intake. Diastolic blood pressure in the supine position was significantly higher on the low than on the medium or high salt diets. 5. Both plasma noradrenaline concentrations and plasma renin activity were significantly higher on the low than on the high salt diet. Values on the medium salt intake were intermediate. Plasma concentrations of both hormones were higher in the upright than in the supine posture on all three salt intakes. 6. The data are consistent with the hypothesis that atrial natriuretic peptide contributes to the cardiovascular and renal adjustments to changes in dietary sodium chloride, and the possible role of the peptide is discussed.

1. The effects of replacing a 1% NaCl drinking solution with Na + -free water for 2 days on body weight and fluid and electrolyte balances were studied in adrenalectomized and sham-operated rats. 2. Eight weeks after operation, after the animals had been drinking Na + -free water for 2 days, some adrenalectomized animals (about 75%; designated group 1) experienced body weight losses which were outside the 99% confidence limits for the sham-operated rats (– 9.2 to + 5.3 g) whereas the remainder (designated group 2) were indistinguishable from the controls. 3. The body weight loss in group 1 was associated with negative fluid, Na + and K + balances. In group 2 rats, fluid balance was maintained as well as in the sham-operated rats, but their handling of Na + and K + was different. 4. In a separate experiment, plasma aldosterone, corticosterone, catecholamine and solute concentrations were measured in adrenalectomized rats from groups 1 and 2 (selected on the basis of body weight loss whilst drinking Na + -free water) and sham-operated rats, after drinking Na + -free water for 2 days. 5. In group 1 animals, plasma aldosterone levels were unmeasurable and corticosterone was extremely low (less than 5% of controls). In group 2, aldosterone was measurable but low, and corticosterone was higher than in group 1 but lower than in sham-operated rats. In line with these findings, animals in group 1, but not those in group 2, were hyponatraemic and hyperkalemia These results are consistent with the activation of latent adrenocortical tissue in the group 2 animals. 6. We suggest that monitoring body weight changes resulting from drinking Na + -free water for 2 days provides a useful, non-invasive test for reliably distinguishing between those adrenalectomized animals with and those without adrenocortical insufficiency.

1. These experiments examined the effects of a high NaCl diet on (Na + , K + )-ATPase in kidney, heart and cerebral cortex, on the level of circulating inhibitor of (Na + , K + )-ATPase in plasma, and on stimulation of (Na + , K + )-ATPase by treatment with dextro ( d )-amphetamine. 2. High salt diet increased indices of (Na + , K + )-ATPase activity (K + -activated p -nitrophenylphosphatase activity and ouabain binding) in kidney medulla, prevented stimulation by amphetamine in cerebral cortex and reduced amphetamine stimulation in heart. 3. High NaCl feeding increased the plasma level of circulating inhibitor of (Na + , K + )-ATPase. 4. Amphetamine alone had no effect on inhibitor level but amphetamine administration reduced the increase in inhibitor with high NaCl feeding.

1. Intravascular coagulation in the kidneys of rats was induced by intravenous infusion of thrombin and by inhibition of fibrinolysis with tranexamic acid under α-chloralose anaesthesia. The amount of fibrin in the kidneys was measured with radioactively labelled fibrinogen. Chronic saline loading and inhibition of angiotensin II (ANG II) with saralasin reduced the fibrin deposition in the kidneys. Infusion of ANG II had the opposite effect. 2. Renal and aortic blood flows were measured by injection of radioactively labelled microspheres. After thrombin infusion the renal and aortic blood flows were reduced to about one-third of the pre-infusion values. Chronic saline loading diminished these changes, but saralasin had no effect. 3. Plasma renin activity (PRA), measured by radioimmunoassay, decreased by about 50% after thrombin infusion. 4. The reduction in PRA and the lack of effect of saralasin indicate that the renin—angiotensin system is not the mediator of the observed decrease in the renal blood flow. As saralasin reduced the amount of fibrin the mechanism regulating fibrin deposition appears to be independent of the mechanism that reduces the renal blood flow.

1. Sequential changes in the ionic composition of the aorta and skeletal muscle were followed during 1, 2 and 4–6 weeks in 30 rats given deoxycorticosterone (DOC) and salt supplemented with potassium chloride. Twenty-one rats, drinking water, were used as controls. 2. Twenty-five per cent of the test rats were hypertensive after 1 week, 60% after 2 weeks and 100% after 4–6 weeks. 3. Muscle potassium fell in all test rats by an average of 15%. In contrast, aortic potassium fell by 19% only in those rats which did not develop hypertension after 1 week. 4. Total and non-inulin sodium and water of the aorta were normal in rats which remained normotensive after 1 or 2 weeks and high in those which became hypertensive during the same period. 5. Total sodium and water content of the aorta were also high in rats which were hypertensive at 4–6 weeks. However, because of simultaneous expansion of the inulin space, non-inulin fractions were normal in this group. 6. Results suggest that vascular ionic changes participate in the pathogenesis of DOC-salt hypertension through more than a single mechanism.

1. The aim of this study was to test whether a postulated gastrointestinal or portal monitor of sodium intake plays any part in adjusting renal sodium excretion when dietary sodium is reduced. 2. Normal male subjects were given 50 mmol of sodium chloride intravenously three times daily for 3 days to replace or to supplement a constant oral intake of sodium chloride. 3. When oral sodium chloride was replaced with intravenous sodium chloride, renal sodium excretion remained constant. 4. When oral sodium chloride was kept constant, sodium administered as intravenous sodium chloride was promptly excreted in three out of four subjects. There was a delay in the increase in sodium excretion in the fourth subject. 5. Infusions containing 50 mmol of sodium chloride in 50 ml given intravenously over 22 min produced a rise in plasma sodium concentration and a fall in concentration of total plasma solids. 6. These results provide no evidence for a gastrointestinal or portal monitor of sodium intake, but do not disprove the existence of such a monitor.

1. The effect of extracellular volume expansion (ECVE) during water diuresis, and of water diuresis alone, on the formation of free water in man was compared. 2. ECVE reduced free water formation at any given rate of distal delivery compared with water diuresis. Thus, ECVE depresses distal sodium chloride reabsorption. 3. This attenuation of free water formation occurred both when urine flow ( V /100 ml glomerular filtration rate) and distal chloride delivery [( C water + C Cl )/100 ml glomerular filtration rate] were used as the terms for distal delivery. 4. We suggest that the distal depression of sodium chloride reabsorption after ECVE is probably due to a direct inhibition of distal sodium chloride transport mechanisms, and not to the flooding of the diluting site by the poorly reabsorbable bicarbonate ion.

1. The role of renal medullary prostaglandin E has been examined in rats with hypertension induced by sodium chloride and deoxycorticosterone (salt—DOC). 2. Synthesis of prostaglandin E was normal in early salt—DOC hypertension. Indomethcin exacerbated the hypertension, and depressed synthesis of prostaglandin E equally in hypertensive and control rats. 3. Synthesis of prostaglandin E was depressed in rats with late salt—DOC hypertension. 4. The results lend support to the concept that prostaglandin E is involved in the regulation of arterial pressure.