Research Division of the Cleveland Clinic Foundation ad the Frank E. Bunts Educational hstitute, Cleveland, Ohio s INCE THE TIME OF RICHARD BRIGHT the kidney has been suspected of being the cause of arterial hypertension, but the theory has waxed and waned to an altogether extraordinary degree. In 1898 Tigerstedt and Bergman1 (304) published a paper demonstrating that crude saline extracts of kidney were pressor when injected into anesthetized rabbits. They thought the active substance in these extracts was a direct vasoconstictor. Even though it was unpurified and unidentified, they called it ‘renin.’Many years passed before any attention was given to this work. It is di&ult to pinpoint when interest in the mechanism of hypertension in the modern sense began (212). By about 1926, it was beginning to be manifest. Volhard (31 I) probably played a significant part with his advocacy of ‘pale’hypertension and its relationship to nephrosclerosis. This was followed in 1984 by the important demonstration by Goldblatt et al.(103) of stable, reproducible hypertension of renal origin in dogs. In retrospect, this was curiously described only as systolic hypertension produced by means of ‘renal ischemia.’This left no doubt, along with other contemporary work, that hypertension could be produced by changing renal hemodynamics. Further, it was soon evident that renal hypertension could be produced even after total sympathectomy (Freeman and Page, 92) or after section of the spinal cord at the level of C& (Glenn, Child, and Page, 100).

We shall deliberately avoid reference to renin in this review whenever possible, as it is a subject worthy of review in itself. This enzyme, in a way, began the story of renal hypertension. Most of the early qerimental work was done with highly impure, and often very small amounts, of the enzyme. It is impossible to distinguish in many cases the action of the enzyme from that of the impurities. Important, also, is whether it is justifiable to attribute any of the observed phys-