How ACE inhibitors transformed the renin‐angiotensin system

The renin-angiotensin-system (RAS) now underlies the successful treatment of almost 50% of the patients in cardiovascular medicine, with serious possibilities of extension to diabetes, Alzheimer's disease and cancer. This clinical transformation started just over 50 years ago, with the unexpected identification of a bradykinin potentiating peptide from snake venom, as a potent inhibitor of angiotensin converting enzyme which led to the development of the first synthetic inhibitor, captopril, followed by the angiotensin receptor blockers. This article analyses the transformation of the RAS into its different stages, from academic experiments to clinical use and back to the laboratory, identifying the critical events involved, both clinical and scientific. The analysis also assesses the contributions of chance, coincidence and conviction that were crucial in this transformation. Although questions remain, the transformation of the RAS over the past five decades provides a success story for Medicine, for Pharmacology and, most significantly, for patients.