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Review: What Signals the Kidney to Release Renin?

• Much has been said and much has been written on the renin-angiotensin-aldosterqne system but one of the most important problems remains unresolved. The specific signals perceived by the renal juxtaglomerular (JG) cells to secrete renin are still unknown. In an editorial in 1964 (1), attention was called to the paucity of experimentation in this area. There is now no lack of interest in and pursuit of this important problem, and recently a number of innovative approaches have resulted in pertinent new data. This article is written to describe these new approaches and to stimulate interest and further research which might close this important gap in our knowledge. Early attempts at elucidation of this problem were aimed at testing either the baroreceptor hypothesis or the macula densa theory. Increasing evidence has accumulated to support the idea that the sympathetic nervous system is also involved. And, a number of humoral agents influence renin release, espedally in pharmacologic doses; these findings raise the question of the physiological roles of these substances in the control of renin secretion. The JG cells, the macula densa, and the renal sympathetic nerves are depicted diagrammatically in relation to the renal arterioles (Fig. 1). In homeostasis and in several experimental and clinical situations with secondary aldosteronism, the renin-angiotensin-aldosterone