Historical perspectives on the renin-angiotensin-aldosterone system and angiotensin blockade

Advances leading to recognition of the relation of the renin-angiotensin system to aldosterone include: (1) development of analytic techniques for measuring aldosterone, (2) discovery of an aldosterone-stimulating factor in circulating plasma, (3) the finding that a potent aldosterone-stimulating factor is secreted by the kidney, (4) evidence that synthetic angiotensin II increases aldosterone secretion, (5) fractionation of crude kidney extracts and the finding that aldosterone-stimulating factor is renin, (6) the observation that high plasma renin activity occurs in secondary aldosteronism, and (7) recognition that the renin-angiotensin-aldosterone system occurs in congestive heart failure and in renovascular and malignant hypertension. The early use of blocking agents for the renin-angiotensin system is described along with the landmarks of progress. These include the observations that: (1) arterial pressure decreases in experimental renovascular hypertension in response to angiotensin blockade, (2) angiotensin provides important support for arterial pressure in low cardiac output states including congestive heart failure, (3) the kidney participates in this important compensatory mechanism, and (4) cellular receptors for angiotensin are present in the two inner zones of the adrenal cortex.