Aprocitentan, a dual endothelin-1 (ET-1) antagonist for treating resistant hypertension: Mechanism of action and therapeutic potential

Jingjing Xu; Xiaohua Jiang; Suowen Xu

doi:10.1016/j.drudis.2023.103788

Aprocitentan, a dual endothelin-1 (ET-1) antagonist for treating resistant hypertension: Mechanism of action and therapeutic potential

Drug Discov Today. 2023 Nov;28(11):103788. doi: 10.1016/j.drudis.2023.103788. Epub 2023 Sep 22.

Authors

Jingjing Xu¹, Xiaohua Jiang², Suowen Xu³

Affiliations

¹ Department of Endocrinology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui 230001, China; Department of Obstetrics and Gynecology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui 230001, China.
² Department of Obstetrics and Gynecology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui 230001, China. Electronic address: biojxh@ustc.edu.cn.
³ Department of Endocrinology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui 230001, China. Electronic address: sxu1984@ustc.edu.cn.

PMID: 37742911
DOI: 10.1016/j.drudis.2023.103788

Abstract

Hypertension is reaching epidemic proportions worldwide and is a significant public health concern. However, ∼15% of patients with hypertension continue to experience elevated blood pressure, even after taking antihypertensive medications [such as angiotensin II receptor blockers (ARBs), angiotensin-converting enzyme inhibitors (ACEIs), dihydropyridine calcium channel blockers (CCBs) and thiazide diuretics], a condition referred to as resistant hypertension (RH). Within the complex realm of blood pressure regulation and vascular function, endothelin-1 (ET-1), a potent vasoconstrictor, plays a pivotal role. Recent research, particularly a Phase III clinical trial (NCT03541174), has shed light on the potential of aprocitentan, a dual ET-1 receptor antagonist, in significantly lowering blood pressure in individuals with RH. In this review, we summarize the mechanism of action and therapeutic potential of aprocitentan as an innovative approach for treating RH.

Keywords: aprocitentan; endothelin-1; hypertension; resistant hypertension.

Publication types

Review

MeSH terms

Angiotensin Receptor Antagonists / therapeutic use
Angiotensin-Converting Enzyme Inhibitors* / therapeutic use
Antihypertensive Agents / pharmacology
Antihypertensive Agents / therapeutic use
Endothelin-1
Humans
Hypertension* / drug therapy
Pyrimidines*
Sulfonamides*

Substances

Angiotensin-Converting Enzyme Inhibitors
aprocitentan
Endothelin-1
Angiotensin Receptor Antagonists
Antihypertensive Agents
Pyrimidines
Sulfonamides