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Title: Studies of leucocyte sodium transport in essential hypertension
Author: Heagerty, A. M.
Awarding Body: University of Leicester
Current Institution: University of Leicester
Date of Award: 1986
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A method was set up and validated to allow the study of sodium efflux in human peripheral blood leucocytes. In view of a postulated association between dietary salt ingestion and the genesis of essential hypertension, movements of sodium were studied across the plasma membranes of leucocytes in hypertensive patients and their normotensive offspring. In hypertensive patients there were small reductions in ouabain resistant and ouabain sensitive efflux rate constants for sodium and a slightly elevated intraleucocytic sodium content. Absolute sodium efflux rates were therefore unchanged compared to control subjects. In the offspring of hypertensive patients, a similar pattern was observed at a time when these subjects had normal blood pressure. In a subsequent series of experiments strong correlations were demonstrated between sodium efflux rate constants in leucocytes and human resistance blood vessels, and in the light of this finding the experiments using leucocytes were extended. In order to test the hypothesis that there is a humoral factor in hypertension that promotes raised blood pressure by inhibition of the Na+/K+ ATPase pump, two experiments were performed: one altered sodium balance by the use of diuretics. In control subjects sodium transport and blood pressure were unaffected, and in normotensive offspring of hypertensives sodium pump activity was stimulated with no change in blood pressure. In the other experiment, similar groups of subjects were exposed to extremes of sodium intake. There were small changes in leucocyte sodium efflux, and a different pattern of response was observed between control subjects and the normotensive offspring of essential hypertensives. In neither of these two experiments were the results compatible with the presence of a circulating sodium pump inhibitor. The existence of abnormalities of transmembrane sodium handling in individuals with a family history of raised blood pressure, at a time when their blood pressure is normal, dissociates these disturbances from the cellular processes that intimately control blood pressure. In addition manoeuvres designed to expand or contract plasma volume by manipulating sodium balance produced changes in sodium efflux incompatible with the promotion of a humoral sodium transport inhibitor. The changes obtained were more compatible with the presence of a disturbance of a genetically predetermined perturbation in the physicochemical structure and function of the cell membrane of which these findings are but one manifestation.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (M.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available