Volume homeostasis, renal function and hypertension

A generalised vasoconstriction, for almost a century believed to be the basis of all types of human hypertension, was disproved by recent haemodynamic studies. In our investigation of hypertension in chronic parenchymatous non-uraemic, non-anaemic renal disease, we have established that the earliest haemodynamic abnormality in subjects, of whom over 90% later develop high blood pressure, has actually started while their blood pressure is still normal. This consists of hypervolaemia and a high cardiac output (hyperkinesis) with tissue hyperperfusion. Hypervolaemia is due to a failure of these still normotensive patients to excrete isotonic saline as readily as subjects with completely normal kidneys. The chronic hypervolaemia in these subjects leads to a release of the natriuretic factor which depresses the Na(+)-K(+)-ATPase in the cell membranes and which is responsible for an increase in sodium (and calcium) content of the vascular smooth muscle cells, diminishing their compliance and thus raising the vascular resistance together with the thickening of the vascular wall of the originally hyperperfused vessels. With the disappearance of the vascular adjustment to the increased cardiac output, the blood pressure rises and the ‘pressure diuresis’ restores the circulating blood volume (and the renal homeostatic efficiency) to normal. With a further rise of the peripheral vascular resistance the cardiac output falls. At this late stage of renal hypertension renin may play a contributory role. Thus, the primary abnormality in the chain of events leading eventually to hypertension is a renal inability to maintain a proper balance between sodium intake and output. This suggested pathophysiological mechanism is probably valid in every kind of human hypertension where a reason for such a disturbance is present.