Studies on the Identity of a Vascular Permeability Factor of Renal Origin

Abstract

1. The administration of crude renal extract to bilaterally nephrectomized rats causes an increase in vascular permeability to plasma proteins. This is associated with a fall in plasma volume. The active material resembles the enzyme renin in pressor activity, heat-lability, pH range of activity and molecular size. 2. To test the possibility that renin might be responsible, renin was extracted from rat renal cortical tissue using methods similar to those used for the purification of pig renin: these involved saline extraction, protein precipitation, freeze drying, ion-exchange and gel-filtration. 3. The final preparation had a pressor activity some 300 times that of the initial saline extract and gel-filtration suggested that the molecular size of rat renin is 40 000–50 000. Assay for pressor and vascular permeability activity at selected stages in the purification showed that both activities ran parallel and could not be dissociated. These results provide strong evidence that the vascular permeability factor is in fact renin. 4. Increase in vascular permeability after injection of semi-purified material could still be demonstrated after bilateral adrenalectomy, though the effect was reduced. 5. In all experiments in which vascular permeability was increased and in which blood pressure was measured, a considerable and sustained rise in blood pressure occurred. It is possible that the increase in blood pressure is causally related to the increase in permeability.