Membrane Handling of Calcium in Essential Hypertension

Several abnormalities have been described in the blood-cell handling of calcium in patients with hypertension and rats with genetic hypertension. We have suggested elsewhere that the multiple abnormalities of monovalent and divalent ion handling by blood cells in hypertension, which are loosely and variably associated with blood pressure, reflect a global variability of cell membrane lipids. In the light of this suggestion we tested the relevance of decreased membrane binding of calcium by examining basal and maximal calcium binding in hypertensive patients and in normotensive subjects with and without a family history of hypertension. Calcium binding was reduced to a similar degree in both hypertensive subjects and those with a family history of hypertension. To examine the role of membrane lipids we examined calcium binding in relation to erythrocyte membrane composition, and found a negative correlation between the palmitic:linoleic acid ratio and calcium binding. This is consistent with the observation of a reduction in the unsaturated fatty acid, linoleic acid, in the erythrocyte membrane of hypertensive subjects, and this may therefore be of functional significance. In further studies, although there was no net difference in leucocyte cytosolic calcium between essential hypertensive subjects and normotensive controls, there was a positive relationship between leucocyte calcium and membrane palmitic:linoleic acid ratio only in normotensives. To test further the role of membrane lipids in calcium handling we administered linoleic acid (4 g daily safflower seed oil) to 13 normotensive volunteers in a double-blind crossover trial. Four weeks of administration of the linoleic acid produced a significant decrease in leucocyte calcium (P<0.05). It is concluded that the abnormalities frequently demonstrated in calcium handling in hypertension are a marker for a global disturbance of cell membrane physicochemical make-up, probably involving the degree of saturation of the fatty-acid component of membrane phospholipids. The nature of the association with blood pressure remains obscure, although evidence from other work suggests that resistance vessel hypertrophy may be more important than calcium-dependent resistance vessel vasoconstrictor tone.