Translational Success Stories: Angiotensin Receptor 1 Antagonists in Heart Failure

The title of the proposed series of reviews is Translational Success Stories. The definition of "translation" according to Webster is, "an act, process, or instance of translating as a rendering of one language into another." In the context of this inaugural review, it is the translation of Tigerstedt's and Bergman's(1) discovery in 1898 of the vasoconstrictive effects of an extract of rabbit kidney to the treatment of heart failure. As recounted by Marks and Maxwell,(2) their discovery was heavily influenced by the original experiments of the French physiologist Brown-Séquard, who was the author of the doctrine that "many organs dispense substances into the blood which are not ordinary waste products, but have specific functions." They were also influenced by Bright's(3) original observation that linked kidney disease with hypertension with the observation that patients dying with contracted kidneys often exhibited a hard, full pulse and cardiac hypertrophy. However, from Tigerstedt's initial discovery, there was a long and arduous transformation of ideas and paradigms that eventually translated to clinical applications. Although the role of the renin-angiotensin system in the pathophysiology of hypertension and heart failure was suspected through the years, beneficial effects from its blockade were not realized until the early 1970s. Thus, this story starts with a short historical perspective that provides the reader some insight and appreciation into the long delay in translation.