An Extra-adrenal Factor Essential for Chronic Renal Sodium Retention in Presence of Increased Sodium-retaining Hormone.

• For many years it has been recognized that normal human subjects and normal dogs retain salt and water only transiently and fail to develop edema during the chronic administration of large doses of a sodium-retaining hormone such as desoxycorticosterone acetate ( DCA ). Similarly, some Addisonian patients retain Na for only a few days in response to prolonged administration of DCA or aldosterone. During a normal Na intake, Na retention occurs for the first one to two days of DCA injection in dogs and for five to ten days of treatment with DCA in human beings -• but, thereafter, Na excretion returns to normal. This phenomenon has been referred to as the "escape" from the sodiumretaining effects of the hormone. The mechanisms involved in this "escape" have been the subject of considerable research and discussion but the problem remains unresolved. In contrast to the failure of chronic Na retention to occur in the normal dog and in some Addisonian patients with large doses of DCA, adrenalectomized dogs with thoracic inferior vena cava constriction ° or with severe pulmonic stenosis show virtually complete Na retention and accumulate ascites for weeks to months during administration of large amounts of DCA. Following removal of the caval ligature in adrenalectomized dogs, Na retention failed to occur despite the administration of six times the minimal maintenance dose of DCA. The presence of a caval ligature or of changes associated with depressed