Orally Active Kidney Extracts and Oils

In order to produce persistent hypertension in animals, it is necessary to restrict the blood flow in both kidneys or to clamp one renal artery and remove the contralateral normal kidney. The presence of a normal kidney seems to have a protective action against the development of severe hypertension. Tigerstedt and Bergman (176) pointed out that the pressor effect of renin was more marked and prolonged in rabbits which had undergone nephrectomy than in normal rabbits. Merrill, Williams, and Harrison (114) found that this increased sensitivity to renin did not appear immediately after removal of the kidneys but developed several days later. The hypothesis was advanced that the body normally contains some substance elaborated by the kidneys which antagonizes the pressor action of renin and which gradually disappears from the body after nephrectomy. 

The search for this hypothetical renal antipressor agent led to the preparation of kidney extracts (65,70,71) which lowered the blood pressure in hypertensive rats and dogs (72,77,189) and showed also some activity in several patients with essential hypertension (72). The authors themselves did not regard the results on hypertensive patients as convincing (73). The active fraction was protein-free but could be precipitated by ammonium sulfate. Parenteral administration was frequently accompanied by toxic effects (77) and the material was therefore administered orally. Even then, however, undesirable symptoms were often observed after the administration of large doses (189). There is no proof that this dialyzable, orally active material constitutes an antipressor factor of the normal kidney. It remains to be seen whether hypertension Is due to a deficiency in an essential humoral agent. 

The material needed to treat one patient for one week required the processing of about eight hundred pounds of kidneys, so that kidneys cannot be considered a practical source for a therapeutic agent of this type. In a search for better sources, it was found (66) that certain marine oils and tung oil contain a depressor substance (Figs. 5, 6). The active ma- 

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