How ACE inhibitors transformed the renin–angiotensin system

Abstract

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 bradykininpotentiating peptide from snake venom, as a potent inhibitor of ACE 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.

Hairless canary seeds (Phalaris canariensis L.) as a potential source of antioxidant, antihypertensive, antidiabetic, and antiobesity biopeptides

“…ACE raises blood pressure by converting angiotensin-I released from the hydrolysis of angiotensinogen by renin into a precursor of vasoconstriction angiotensin II (Pihlanto-Leppälä 2000). Synthetic ACE inhibitors have been utilized as potent oral antihypertensive drugs for years (Bakhle 2020); however, research has identified that plant constituent (e.g., peptides, terpenoids, alkaloids, tannins, proanthocyanidins, and flavonoids) can serve as a natural source of ACE inhibitors (R. Kumar et al 2010). Small molecular weight peptides, for instance, have demonstrated a strong inhibitory capacity compared to other natural macromolecules (Alcaide-Hidalgo et al 2020).…”

Genetic Hypothesis and Pharmacogenetics Side of Renin-Angiotensin-System in COVID-19

“…Escaping mechanisms associated with prolonged ACEi treatment, aiming at restoring Ang-II levels, have been recognized. The available drugs include Captopril, used in clinical practice since the 1980s, Benazepril, Enalapril, Fosinopril and many others commercially released over time [ 104 ].…”

The Human-Covid Tango: Connecting the Dots

“…Bradykinin is a proinflammatory proliferative peptide hormone inducing vasodilation, vascular permeability and edema (Kempe et al,2020;Lopatko et al,2019;Pé terfi et al,2019). Bradykinin is upregulated by ACE inhibitors (Bakhle, 2020) and may be playing a significant role that has gone unnoticed in the Covid-19 saga. We will review all three components with regards to Covid-19, discussing the main ideas being published and conclude with elucidation of future directions in this field.…”