History of Angiotensin Research
| Category | Research |
|---|---|
| Also known as | angiotensin history, renin angiotensin system, hypertensin |
| Last updated | 2026-04-14 |
| Reading time | 3 min read |
| Tags | historyangiotensinreninhypertensioncardiovascular |
Overview
Angiotensin refers to a family of peptides produced through sequential enzymatic cleavage of the liver-derived precursor angiotensinogen. The most familiar, angiotensin II, is an eight-amino-acid peptide that is a potent vasoconstrictor and stimulates aldosterone release from the adrenal cortex, making it a central player in blood pressure and fluid balance regulation.
The angiotensin system's unravelling involved parallel work in Argentina and the United States. In Argentina, Bernardo Houssay, Juan Carlos Fasciolo, and Eduardo Braun-Menéndez identified a vasoconstrictor substance from renal extracts they called "hypertensin." In the United States, Irvine Page at the Cleveland Clinic and his colleagues identified a similar substance they called "angiotonin." In 1958, the two groups agreed to combine the names into "angiotensin," resolving a long-running terminological dispute.
Subsequent work over the 1960s and 1970s established the cascade: renin, an enzyme secreted by the juxtaglomerular cells of the kidney, cleaves angiotensinogen to produce angiotensin I; angiotensin-converting enzyme (ACE) converts angiotensin I to angiotensin II; angiotensin II acts through AT1 and AT2 receptors to produce its cardiovascular effects. Additional components such as angiotensin (1-7), angiotensin III, angiotensin IV, and ACE2 further diversify the system.
Key People
- Bernardo Houssay (1887–1971): Argentine physiologist and 1947 Nobel laureate (for other work) who supervised the angiotensin studies.
- Juan Carlos Fasciolo and Eduardo Braun-Menéndez: Argentine physiologists who identified "hypertensin."
- Irvine H. Page (1901–1991): American scientist who identified "angiotonin" at the Cleveland Clinic.
- Franz Gross and John Laragh: Contributed to the clinical understanding of the renin-angiotensin system.
- David Cushman and Miguel Ondetti: Developed captopril from snake venom peptides.
Timeline
- 1898: Tigerstedt and Bergman describe a renal pressor substance, "renin."
- 1939–1940: Argentine and American groups independently identify angiotensin.
- 1956: Skeggs and Leloir characterize the angiotensin I-to-II conversion step.
- 1958: "Angiotensin" is adopted as the unified name.
- 1967: Ferreira identifies bradykinin-potentiating factor in snake venom.
- 1977: Captopril, the first ACE inhibitor, is developed.
- 1995: Losartan, the first angiotensin receptor blocker (ARB), is approved.
- 2000: ACE2 is discovered.
- 2017: Synthetic angiotensin II is approved for septic and other distributive shock.
Background
The renin-angiotensin-aldosterone system (RAAS) is among the most thoroughly studied hormonal networks in physiology. It integrates signals from renal perfusion, sympathetic tone, and sodium balance to maintain blood pressure and fluid homeostasis. Dysregulation contributes to hypertension, heart failure, chronic kidney disease, and diabetic nephropathy.
The discovery of the ACE2 axis added new dimensions. ACE2 cleaves angiotensin II to produce angiotensin (1-7), a peptide with largely opposing, protective effects mediated through the Mas receptor. ACE2 also serves as the receptor used by SARS coronaviruses (including SARS-CoV-2) for cell entry, making the angiotensin system a central element of COVID-19 biology.
Modern Relevance
Angiotensin-targeted drugs are among the most widely prescribed cardiovascular medications. ACE inhibitors and angiotensin receptor blockers are first-line for hypertension, heart failure with reduced ejection fraction, diabetic kidney disease, and post-myocardial infarction. Aldosterone antagonists, direct renin inhibitors, and neprilysin/ARB combinations (for example, sacubitril/valsartan) extend the therapeutic options.
On the peptide front, synthetic angiotensin II itself is now approved for vasopressor-refractory distributive shock. Experimental work targets angiotensin (1-7), ACE2, and alamandine, seeking to augment the protective arm of the system. The century-long story of angiotensin research illustrates how peptide chemistry, physiology, and pharmacology combine to reshape clinical medicine. For related systems, see bradykinin-discovery.
Related Compounds
Related entries
- History of Atrial Natriuretic Peptide— Atrial natriuretic peptide was identified in 1981 by Adolfo de Bold, establishing the heart as an endocrine organ.
- The Discovery of Bradykinin— Bradykinin, a central mediator of inflammation and vasodilation, was discovered in 1949 by Rocha e Silva, Beraldo, and Rosenfeld in Brazil.
- The Discovery of Endothelin— Endothelin-1, one of the most potent vasoconstrictors known, was identified in 1988 by Masashi Yanagisawa in Tsukuba.