Reviews in Cardiovascular Medicine (Apr 2025)

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

  • Zhe Jiang,
  • Changlin Zhai,
  • Guanmin Tang

DOI
https://doi.org/10.31083/RCM27963
Journal volume & issue
Vol. 26, no. 4
p. 27963

Abstract

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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).

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