The Birth of Angiotensin: An International Compromise.

Irvine Page in the United States and Eduardo Braun-Menéndez in Argentina led teams of investigators that studied the role of the kidney in blood pressure regulation. Contemporaneously in 1939, each team using different methods discovered and described a new substance now known as angiotensin. At the time of discovery, Page called it "angiotonin" and Braun-Menéndez called it "hipertensina," anglicized to "hypertensin." Over time, the importance of this substance in circulatory control, pathophysiology and pharmacology became indisputable and the need for a single name became obvious. In a remarkable accommodation, Page and Braun-Menéndez agreed to forego any claim to priority and chose a name with elements of both. Following this compromise, Page and Braun-Menéndez went on to become leaders in science in their own countries as well as recognition world-wide while, angiotensin and its derivatives have become standard components in the understanding and treatment of diseases of the heart, kidney and brain.

[History of the renin-angiotensin system: great men, a great finding]. / Historia del sistema renina angiotensina: grandes hombres, un gran descubrimiento.

The discovery of the renin-angiotensin-aldosterone system (RAS) was one of the important findings in physiology. Two research groups, in both North and South America, independently discovered that renin released a novel vasopressor agent. The Argentine group named it hypertensin, and called hypertensinogen to its plasma protein substrate. The group from the United States named it angiotonin. In 1958, Braun Menendez and Irvine Page suggested that the peptide's name should be angiotensin. Development of angiotensin converting enzyme (ACE) inhibitors proved that the RAS is effective in controlling hypertension and heart failure, and in preventing vascular injury in chronic diseases. Both teams, showing that beyond being great investigators they were remarkable persons, shared the merit of the discovery.

A cornerstone in the history of hypertension: the seventieth anniversary of the discovery of angiotensin.

In 1939, two independent teams, in Buenos Aires and Indianapolis, identified the polypeptide angiotensin. In 1934, Goldblatt et al. demonstrated that partial occlusion of the renal arteries produces hypertension in dogs, and Houssay in 1936 predicted the presence of a humoral mechanism and, with Fasciolo, demonstrated that the ischemic kidneys released a pressor substance that increased the recipient's blood pressure. Later on, Taquini proved that the rise in blood pressure that follows the re-establishment of circulation in kidneys was also produced by a plasmatic substance from the venous blood of acute ischemic kidneys and it was called 'hypertensin'. Then, they proved that it was the result of an enzymatic reaction in which renin was the enzyme and plasma the substrate. At the same time, in 1939, Page et al. postulated that renin activated by plasma becomes vasoactive and the substance was called 'angiotonin'. Page's group began in 1937, with the purification of renin, studying its renal hemodynamic effects. Later on, Page et al. acknowledged in 1943 the enzymatic nature of the system and renamed their so-called renin-activator as renin substrate. Both groups fused the two original names into 'angiotensin' during a meeting at Michigan in 1958, making the 'adventure of the discovery of angiotensin' a reality.

The discovery, isolation and identification of aldosterone: reflections on emerging regulation and function.

This paper has a focus on the early history of aldosterone. The Taits take us on a chronological trawl through the history in which they had a first hand role and made a major contribution-their bioassay was in many ways the key. The gifted Swiss chemists made a critical contribution to the scale and isolation of larger amounts. This was international collaboration at its best. Developing technologies were utilised as crucial cutting edge applications in the advancing front, technology transfer before the word was invented. Measurement of aldosterone and angiotensin were crucial advances to the understanding of the regulation of the hormone. In the period 1960-2003, some 30,000 papers mentioned aldosterone as a keyword, even so advances on a larger scale were slow. I have indicated some of my own work with the Howard Florey team using the adrenal autotransplant in the conscious sheep. Recently, the understanding of the role of induced proteins, the flow on from the RALES trial and the development of eplerenone has revitalised the aldosterone field.

Historical perspective of the renin-angiotensin system.

Researchers continue to be fascinated with the renin-angiotensin system (RAS) more than 100 yr after its discovery because of its powerful role in controlling sodium balance, body fluid volumes, and arterial pressure. Development of drugs that block different components of this system has led to powerful treatments for hypertension, heart failure, diabetes, and other diseases. Molecular approaches to studying this system offer new possibilities for better understanding the physiology and pathophysiology of the RAS, and for developing new therapeutic paradigms. Our challenge in the future will be to effectively utilize the technological advances that are taking place in virtually all areas of science, including the RAS, and to translate them into a better understanding of the pathophysiology and treatment of human diseases.

History about the discovery of the renin-angiotensin system.

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. In Buenos Aires, it was called hypertensin; in the United States, angiotonin. In 1958, Eduardo Braun Menéndez from Argentina and Irving H. Page from the United States agreed to name it angiotensin.