Relation of renin and angiotensin II to the control of aldosterone secretion.

• At the Laurentian Hormone Conference in 1958, evidence was presented to show that the immediate stimulus to aldosterone production is humoral. Cross-circulation of blood from dogs with experimental secondary hyperaldosteronism through normal isolated adrenals produced an increase in aldosterone secretion by the isolated adrenals.' This finding suggests that a humoral agent in peripheral blood acts on the adrenals to augment aldosterone secretion. Concurrent independent observations in conscious sheep by Denton, Goding, and Wright provided similar evidence for an aldosterone-stimulating factor in peripheral blood during chronic sodium depletion. It was suggested that this humoral agent is a hormone which has been designated the aldosterone-stimulating hormone (ASH). In 1960, two new findings, which were reported almost simultaneously, suggested the possibility that the renin-angiotensin system is important in the control of aldosterone secretion. First, it was observed that the aldosterone-stimulating hormone is secreted by the kidney' and, secondly, it was reported that synthetic angiotensin II augments aldosterone secretion when given intravenously to man.' The first evidence that ASH is secreted by the kidney was obtained from studies of the effects of systematically removing different areas of the body and, subsequently, determining the response in aldosterone secretion to acute hemorrhage. A positive response to acute blood loss in the absence of the anterior pituitary was considered as presumptive evidence for secretion of ASH. The observations were made in the absence of the anterior pitProm the Section on Experimental Cardiovascular Disease, Laboratory of Kidney and Electrolyte Metabolism, National Heart Institute, Bethesda, Maryland.