Cell membrane phospholipids in the genesis and maintenance of hypertension.

In these studies the structure and metabolism of cell membrane lipids was investigated during the development of human hypertension and in animal models of this disease. Erythrocyte membrane fatty acid profiles were found to be similarly deranged in genetic hypertension prone rats, in human hypertensive patients and their normotensive offspring. Such profiles were found to be readily manipulated in normotensive human volunteers by changes in dietary fat intake; increasing dietary polyunsaturated fat caused a fall in blood pressure and altered membrane sodium handling. In genetically hypertension prone rats polyunsaturated fat induced increases in cell membrane linoleic acid content but did not prevent the development of hypertension suggesting that the amount and the type of fat may be important in blood pressure amelioration. Basal cellular phosphoinositide metabolism was increased in the erythrocytes of normotensive offspring of human hypertensives and in the aortae of young hypertension prone rats. This was not detected in either species in established hypertension. Reduced agonist- induced responses were found in vascular tissue from adult genetically hypertensive rats. It was concluded that in essential hypertension and rat genetic hypertension alterations in plasma membrane fatty acid profiles may underlie abnormalities of membrane function. Increased phosphoinositide metabolism found as hypertension was developing may be a genetically determined mechanism initiating changes to vascular structure and blood pressure. In the rat, coarctation hypertension increased basal vascular phosphoinositide metabolism and the development of aortic smooth muscle cell hypertrophy paralleled the increase in blood pressure, no changes were seen in aorta exposed to reduced pressure. It is concluded that vascular hypertrophy was induced through phosphoinositide metabolism stimulated by increased blood pressure. This may be important in maintaining increased peripheral vascular resistance seen in hypertension.