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Potassium chloride (96 mmol potassium/day) in the form of 12 Slow K tablets/day in 10 patients on an intake of 150 mmol sodium and 80 mmol potassium produced a cumulative sodium loss of 110 mmol by the 12th day of potassium supplementation. At the same time there was attenuation of the expected increase in plasma renin activity appropriate for such a sodium loss. The lack of rise in plasma renin activity and hence angiotensin II combined with sodium loss may account at least in part for the observed blood pressure fall. No change in ouabain-sensitive or total white cell sodium efflux rate constant was found. An effect of an increase in plasma potassium on the sodium pump cannot be excluded as the white cell sodium efflux rate constant was measured in a fixed external potassium concentration. There was no evidence from plasma noradrenaline measurements that increasing potassium intake reduces sympathetic activity in the resting state.

Leucocyte sodium efflux was measured in control leucocytes pre-incubated for 90 min with serum from patients with advanced liver cirrhosis. Serum from patients with advanced alcoholic liver cirrhosis was inhibitory to sodium transport in control leucocytes. The degree of inhibition was similar to that seen in the patients' own leucocytes; the defect induced by patient serum was primarily inhibition of ouabain-insensitive sodium efflux, whereas in the patients' own leucocytes, inhibition was seen in both ouabain-sensitive and -insensitive sodium efflux, as shown previously. The results suggest that a circulating factor, present in patients with advanced cirrhosis, is capable of inhibiting sodium transport in leucocytes.

1. Serum from patients with fulminant hepatic failure inhibits the ouabain-sensitive sodium efflux in leucocytes. A 1 : 100 dilution of the serum was necessary before the inhibition became undetectable. 2. Dialysates of the serum through cuprophane in vitro and polyacrylonitrile haemodialysis in vivo were inhibitory in small amounts. 3. Ultrafiltrates ( less than 10 000 daltons) of serum were chromatographed on Sephadex G-25 and the elution profile obtained from patients with fulminant hepatic failure was both qualitatively and quantitatively different from that of normal controls. Material from peaks 3, 4, 5 and 7 in patients with fulminant hepatic failure inhibited leucocyte sodium transport. 4. dialysate from haemodialysis with the polyacrylonitrile membrane contained most peaks, particularly peaks 4 and 5. Adsorption of serum with polymer coated charcoal in vitro largely removed peaks 5-8.

1. The mineralocorticoid 9 alpha-fluorohydrocortisone was given to 12 patients with cirrhosis without ascites. In seven an 'escape' from its sodium-retaining effects was observed, the other five continuing to retain sodium. 2. Changes in plasma renin activity (PRA) and inulin clearance (Cinulin) were used in the assessment of possible changes in the 'effective' extracellular fluid volume. PRA fell and Cinulin increased to a similar extent in each of the two groups of patients. The findings do not support the concept that the failure to show the mineralocorticoid escape in some patients with cirrhosis is due to a failure of expansion of the effective extracellular fluid volume. 3. Sodium reabsorption in the different segments of the nephron as estimated by clearance techniques under conditions of maximal water diuresis showed that the greatest changes to account for both mineralocorticoid escape and sodium retention were in the part of the nephron beyond the diluting segment.

Intracellular sodium content and ouabain-sensitive sodium efflux rate constant were measured in leucocytes and erythrocytes from subjects with untreated essential hypertension and also in normotensive subjects with and without a family history of hypertension. Leucocytes from hypertensives were again shown to have a higher intracellular sodium content and lower ouabain-sensitive sodium efflux rate constant than normotensive controls but there were no differences between those normotensive subjects with and those without a family history of hypertension. No differences in erythrocyte sodium content or efflux rate constant were seen between any of the three groups.

Dietary sodium restriction (10 mmol Na/day) for a period of 2 weeks did not result in any change in the blood pressure of 12 healthy young adults (mean age 21). There was also no change in their leucocyte sodium transport investigated immediately before the diet and on the last day. Sodium restriction (10 mmol Na/day) in 12 middle-aged hypertensive subjects (mean age 56) for the same period of time caused a significant fall in both systolic and diastolic blood pressure. The leucocyte total sodium efflux rate constant was initially low, but after the diet significantly increased towards the control value. The results are compatible with the theory that a circulating sodium transport inhibitor is present in patients with essential hypertension, and is related to salt intake.

The role of Na-H exchange in endothelin-induced contraction of human peripheral resistance vessels was investigated. Endothelin produced a dose-dependent contraction which was greatly attenuated in the presence of a low extracellular sodium concentration. Inhibition of Na-H exchange by the amiloride analogue 5-(N,N-hexamethylene) amiloride (5-NNHA) resulted in a greater than 65% relaxation of a maximal endothelin-induced contraction in the presence of normal extracellular sodium. However, in the presence of a low extracellular sodium concentration, inhibition of Na-H exchange only resulted in a 25% relaxation. These data suggest that endothelin-induced vasoconstriction of human peripheral resistance vessels is mediated in part by stimulation of Na-H exchange.