History About the Discovery of the Renin-Angiotensin System

Abstract

Abstract-The history of the discovery of the renin-angiotensin system began in 1898 with the studies made by Tigerstedt and Bergman, who reported the pressor effect of renal extracts; they named the renal substance renin based on its origin. In 1934, Harry Goldblatt induced experimental hypertension in dogs by clamping a renal artery. About 1936, simultaneously in the Medical School of the University of Buenos Aires, Argentina, and in the Eli-Lilly Laboratories in Indianapolis, 2 independent groups of researchers, using the Goldblatt technique to produce experimental hypertension, demonstrated renal secretion of a pressor agent similar to renin. In the following years, both teams described the presence of a new compound in the renal vein blood of ischemic kidneys. This agent was extracted from blood with 70% acetone and had a short pressor effect. The final conclusion was that renin acted enzymatically on a plasma protein to produce the new substance. He related hypertrophy to an increased resistance to blood flow in the small vessels due to the altered condition of the blood. In 1868, George Johnson, 2 reporting studies on nephritis, suggested that hyaline-fibroid alterations in the renal vessels were due to an impure condition of the blood, which was also responsible for left ventricular hypertrophy. F.A. Mahomed, 3 using a primitive sphygmograph for the first time, described high blood pressure in 1872. He also linked left ventricular hypertrophy to hypertension due to nephritis and reported the presence of high blood pressure in patients without renal disease. 4,5 Finally, Riva-Rocci, 6 in 1896, described the first indirect sphygmomanometer to measure arterial pressure in humans, and in 1905, Korotkoff 7 defined the sounds that are named after him.The relationship between pathological alterations in the kidney and the development of systemic arterial hypertension had been postulated for many years. In this sense, Franz Volhard 8 suggested the existence of a circulating vasopressor substance. He classified the hypertensive patients: those with slight vascular damage as reds, and those with important vascular lesions-mostly in the kidney, pale skin, and cerebral damage (malignant hypertension)-as white.On the other hand, by the end of the nineteenth century, Tigerstedt, a Finnish professor of physiology working at the Karolinska Institute, and his assistant Bergman 9 analyzed the effect of renal extracts on arterial pressure. They discovered the presence of a pressor compound in the renal tissue of the rabbit, and based on its origin, they named it renin. The pressor activity could be extracted with glycerin, did not dialyze, and was stable at 56°C and was destroyed by boiling. Moreover, they showed that the renal vein blood increased blood pressure when injected into nephrectomized animals. They also detected the potentiation and protraction of the pressor response to renin in the nephrectomized recipient. They explained that the association between renal disease and cardiac hypertrophy was due to the kidney ...

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