1. A method has been developed which makes possible the demonstration of a pressor substance in the circulating systemic blood of dogs with experimental renal hypertension. 2. After the intravenous injection of renin into normal dogs, it was possible to detect a pressor substance formed in the systemic blood. After the intravenous injection of 1 unit of renin, as much as 1 unit of the pressor substance was detected in the plasma from 200 cc. of systemic blood. 3. Large amounts of systemic blood pooled from several normal dogs did not contain detectable amounts of pressor substance. 4. In experimental renal hypertension due to unilateral or bilateral constriction of the main renal arteries, a pressor substance was demonstrated in large amounts of systemic blood, corresponding to from one-fifth to one-third of the total blood volume. This was accomplished without the addition of hypertensinogen to enhance the action of the renin in the blood. In an animal weighing about 15 kilos, with benign hypertension up to 3 months' duration, about 3 to 5 units of this pressor substance are probably constantly circulating in the entire systemic blood. 5. The pressor substance was also detected in a relatively small amount of renal vein blood from an ischemic kidney. 6. In the systemic blood of dogs weighing about 15 kilos, with malignant experimental renal hypertension, from 15 to 25 units, or more, of the pressor substance are present in the entire circulating blood. 7. The pressor substance which appears in the systemic blood of dogs with experimental renal hypertension, and of normal dogs after intravenous injection of renin, is destroyed by hypertensinase. 8. The pressor substance obtained from the systemic blood of dogs with experimental renal hypertension has the same physiological and chemical properties as hypertensin produced in vitro . It is therefore suggested that the name hypertensin be adopted for the pressor substance which causes experimental renal hypertension. 9. In this study the animals in the benign phase of hypertension were almost all in the early stage (3 months or less). Whether the humoral mechanism obtains in animals in the late stage, after years of hypertension, or in any form of human hypertension is being investigated.
Many plants contain an enzyme similar in most biological properties to the hypertensinase obtained from blood and some animal tissues, notably kidney and intestinal mucosa. Wheat bran is a rich source of the plant hypertensinase, and from it a potent, non-toxic preparation was made by the use of isoelectric and ammonium sulfate precipitation as the means of purification. Hypertensinase derived from bran and administered intramuscularly was not absorbed, or was absorbed only very slowly, into the blood plasma. Repeated intramuscular injection of large quantities of plant hypertensinase did not reduce the blood pressure of dogs with experimental renal hypertension. The intravenous injection of large quantities of plant hypertensinase into dogs resulted in an immediate increase in the content of hypertensinase in the plasma. Dogs with a high hypertensinase level in the plasma failed to react, or reacted much less markedly to the intravenous injection of amounts of renin or hypertensin which had previously proved effective. The slow intravenous injection of plant hypertensinase into a dog with experimental renal hypertension reduced the blood pressure to the normal level for the period during which the concentration of plant hypertensinase in the blood was considerably elevated. After the return of the hypertensinase of the plasma to normal, the blood pressure rose again to its previously high level. Inactivated plant hypertensinase did not increase the hypertensinase content of the plasma, did not interfere with the action of renin and hypertensin, and did not reduce the high blood pressure of dogs with experimental renal hypertension. In a dog with an increased level of plasma hypertensinase, the pressor substance hypertensin could still be detected in the systemic blood immediately after the intravenous injection of renin in an amount to which the animal responded with only a slight rise in blood pressure.