Studies of erythrocyte sodium transport in essential hypertension.

This thesis reports studies of erythrocyte membrane sodium handling in untreated patients with essential hypertension, their normotensive offspring and normotensive subjects with no family history of hypertension. Normotensive subjects were studied on their normal diet and after dietary manipulation of sodium, potassium and fat intake. Patients with essential hypertension had a significantly increased erythrocyte sodium and total sodium efflux rate constant but the absolute flux rate was not significantly different. Similar trends were observed in the normotensive offspring of hypertensive patients but none of the components achieved statistical significance. In the normotensive subjects a number of dietary manipulations were undertaken. The first involved an attempt to expand plasma volume using a high salt intake to try and induce inhibition of the glycoside sensitive sodium efflux. This was not observed: in addition a reduction of sodium efflux rate constant was observed when the salt intake was lowered. Furtheremore, there was a qualitative difference in the pattern of response to dietary change when control subjects with no family history of hypertension were compared to those subjects with one or more first degree hypertensive relatives. Similarly, supplementation of the normal omnivore diet with potassium revealed a qualitative difference in response in erythrocyte sodium transport in the controls and that seen in offspring of hypertensive patients. In view of the possibility of an intrinsic membrane abnormality underlying these qualitative differences, an attempt was made to change sodium membrane handling by supplementing the diet with polyunsaturated fat (linoleic acid) which was subsequently shown to be incorporated into the erythrocyte membrane. Small changes in sodium transport were observed but these did not achieve statistical significance in either the offspring of hypertensive subjects or controls. However, a significant fall in systolic blood pressure was observed in the control subjects. These studies are inconsistent with a single humoral factor having a profound effect upon membrane sodium handling but are in keeping with an alternative hypothesis that there is a genetic abnormality of physicochemical structure and function of the plasma membrane in essential hypertension.