E. M. Clarkson

Evidence for a circulating sodium transport inhibitor in essential hypertension.

The active sodium transport of white cells and red cells obtained from patients with essential hypertension was impaired. Incubating white cells from normotensive subjects in serum obtained from patients with essential hypertension caused an impairment in sodium transport in the white cells of normotensive subjects similar to that found in the white cells of hypertensive patients. The impairment in sodium transport was due to a fall in the ouabain-sensitive component of the total sodium efflux rate constant. These results show that the serum of patients with essential hypertension contains a substance which influences sodium transport and that it has ouabain-like activity. They also suggest that it is this substance which causes the impairment in sodium transport in the leucocytes of patients with essential hypertension. These findings support the hypothesis that the rise in blood pressure in patients with essential hypertension is due to an increased concentration of a circulating sodium transport inhibitor which is continuously correcting a tendency for sodium retention by the kidney.

EFFECT OF SODIUM INTAKE ON ABILITY OF HUMAN PLASMA TO INHIBIT RENAL Na+-K+-ADENOSINE TRIPHOSPHATASE IN VITRO

Abstract An inhibitor of renal sodium-potassium-dependent ATPase was demonstrated in human plasma by a cytochemical technique. Circulating levels of this activity were 25 times greater in plasma taken when five healthy subjects were on a high-salt diet than in plasma obtained when they were on a low-salt diet. These results are consistent with the proposal that urinary sodium excretion is in part controlled by a circulating natriuretic substance.

Observations on A, Low Molecular Weight Natriuretic and Na-K-ATPase Inhibitory Material in Urine

Natriuretic and Na-K-ATPase inhibitory material prepared from urine by gel filtration on G25 Sephadex was previously found to be of low molecular weight, polar and non-peptide. Although activity appeared to depend on an amino group, tests and radioenzymatic assays for catecholamines suggested that these were not implicated in the natriuretic activity. Further purification of the material included solvent extraction, cation exchange and high performance liquid chromatography. At each stage, fractions were assayed for natriuretic activity, stimulation of G6PD and inhibition of Na-K-ATPase in cytochemical assays, and for digoxin-like activities i.e. inhibition of dog kidney Na-K-ATPase (Sigma), displacement of 3H ouabain bound to cell membranes and cross reaction with antidigoxin antibody. The crude material possessed all activities, but with successive purifications the activities separated from each other and were thus due to different substances. Analyses for catecholamines with HPLC and electrochemical detection revealed that the natriuretic activity was due to dopamine.

Slow sodium: an oral slowly released sodium chloride preparation.

The use of a slowly released oral preparation of sodium chloride is described. It was given to patients and athletes to treat or prevent acute and chronic sodium chloride deficiency. Gastrointestinal side effects were not encountered after the ingestion of up to 500 mEq in one day or 200 mEq in 10 minutes.

Evidence for a Hormone other than Aldosterone which Controls Urinary Sodium Excretion

This chapter discusses evidences for a hormone other than aldosterone, which controls urinary sodium excretion. The evidence suggests that changes in extracellular fluid volume also involve a change in the circulating concentration of a hormone other than aldosterone that controls urinary sodium excretion. From these observations, it appears that in the urine of the salt loaded subject, there occurs a change in the concentration of some substance, which is none of these hormones. In conclusion, it appears that in both the blood and the urine of animals, which have been expanded with saline or blood there is a substance other than aldosterone that influences urinary sodium excretion.