Novel Antihypertensive Medications to Target the Renin-Angiotensin System: Mechanisms and Research.

An estimated 1.28 billion individuals in the global population suffer from hypertension. Importantly, uncontrolled hypertension is strongly linked to various cardiovascular and cerebrovascular diseases. The role of the renin-angiotensin system (RAS) is widely acknowledged in the development and progression of hypertension. This system comprises angiotensinogen, the renin/(pro)renin/(pro)renin receptor (PRR) axis, the renin/angiotensin-converting enzyme/angiotensin (Ang) II/Ang II type I receptor (AT1R) axis, the renin/angiotensin-converting enzyme (ACE) 2/Ang (1-7)/Mas receptor (MasR) axis, the alamandine/Mas-related G protein-coupled D (MrgD) receptor axis, and the renin/ACE/Ang II/Ang II type II receptor (AT2R) axis. Additionally, brain Ang III plays a vital role in regulating central blood pressure. The current overview presents the latest research findings on the mechanisms through which novel anti-hypertensive medications target the RAS. These include zilebesiran (targeting angiotensinogen), PRO20 (targeting the renin/(pro)renin/PRR axis), sacubitril/valsartan (targeting the renin/ACE/Ang II/AT1R axis), GSK2586881, Ang (1-7) and AVE0991 (targeting the renin/ACE2/Ang (1-7)/MasR axis), alamandine (targeting the alamandine/MrgD receptor axis), C21 and β-Pro7-Ang III (targeting the renin/ACE/Ang II/AT2R axis), EC33, and firibastat and NI956 (targeting brain Ang III).