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Related Concept Videos

Treatment for Pulmonary Arterial Hypertension: Endothelin Receptor Antagonists01:18

Treatment for Pulmonary Arterial Hypertension: Endothelin Receptor Antagonists

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Endothelins (ETs) are potent vasoactive peptides critical in the human body's various physiological and pathological processes. One of the most promising therapeutic strategies for treating pulmonary arterial hypertension (PAH) involves counteracting the effects of these endothelins using a class of drugs known as endothelin receptor antagonists.
ETs are synthesized through a complex sequence of enzymatic steps, primarily involving an enzyme referred to as endothelin-converting enzyme...
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Treatment for Pulmonary Arterial Hypertension: Prostacyclin Receptor Agonists01:23

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Prostacyclin receptor agonists are a class of therapeutic agents integral to managing pulmonary arterial hypertension (PAH). These drugs operate by mimicking the action of prostaglandin I2, or PGI2, a naturally occurring compound in the body.
These agonists bind to the IPR receptor situated on the plasma membrane of the pulmonary artery smooth muscle cells. This binding triggers a cascade of reactions known as the GS-AC-cAMP-PKA pathway. This pathway results in the relaxation of smooth muscle...
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Heart Failure Drugs: Inhibitors of Renin-Angiotensin System01:26

Heart Failure Drugs: Inhibitors of Renin-Angiotensin System

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The activation of the sympathetic nervous system and the renin-angiotensin-aldosterone system (RAAS) contributes to cardiac remodeling, and inhibiting the RAAS is a pharmacological target in heart failure management. As a result, neurohumoral modulation is a crucial treatment principle for managing heart failure. This approach involves using medications like ACE inhibitors (ACEIs), angiotensin receptor blockers (ARBs), β-blockers, mineralocorticoid receptor antagonists (MRAs), and neutral...
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Treatment for Pulmonary Arterial Hypertension: Receptor Tyrosine Kinase Inhibitors and Calcium Channel Blockers01:26

Treatment for Pulmonary Arterial Hypertension: Receptor Tyrosine Kinase Inhibitors and Calcium Channel Blockers

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Receptor tyrosine kinase inhibitors (TKIs) and calcium channel blockers (CCBs) are two critical categories of drugs employed in the treatment of pulmonary artery hypertension (PAH). PAH is a disease that causes high blood pressure in the pulmonary arteries, resulting in chest pain, fatigue, and shortness of breath.
TKIs, such as imatinib (Gleevec), are particularly effective in tackling the growth and mitogenic factors that become upregulated in PAH patients. These factors contribute to the...
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Antihypertensive Drugs: Direct Renin Inhibitors01:25

Antihypertensive Drugs: Direct Renin Inhibitors

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The renin-angiotensin-aldosterone system (RAAS) is an intricate physiological pathway involving numerous enzymes and hormones, including renin, angiotensin-converting enzyme (ACE), angiotensin I and II, and aldosterone. Imbalances within this system increase the production of angiotensin II and aldosterone. Increased angiotensin II levels promote vasoconstriction and blood pressure elevation. Concurrently, higher aldosterone levels stimulate sodium and water reabsorption in the kidneys,...
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Antihypertensive Drugs: Angiotensin II Receptor Blockers01:30

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In the renin-angiotensin-aldosterone system, a hormone called angiotensin II plays a crucial role. It binds to the AT1 receptors in vascular smooth muscles coupled with Gq proteins. The activation of these receptors activates an enzyme called phospholipase C, which releases two molecules: inositol trisphosphate and diacylglycerol. These molecules cause a chain reaction that leads to the phosphorylation of myosin light chains and promotes interaction between actin and myosin, leading to smooth...
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Updated: Jan 7, 2026

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A New Drug for Resistant Hypertension: Aprocitentan.

Jaspreet Kaur Sidhu1, Deepti Chopra2, Abhinav Goyal1

  • 1Department of Pharmacology Amrita School of Medicine, Amrita Vishwa Vidyapeetham, Faridabad, India.

Current Hypertension Reviews
|January 5, 2026
PubMed
Summary

A new drug, aprocitentan, offers a novel treatment for resistant hypertension by blocking endothelin-1 receptors. This dual endothelin receptor antagonist shows significant blood pressure reduction, especially in high-risk patients.

Keywords:
Aprocitentanantihypertensive agents.dual endothelin-1 receptor antagonistresistant hypertension

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Area of Science:

  • Cardiovascular Medicine
  • Pharmacology
  • Nephrology

Background:

  • Resistant hypertension (RH) is uncontrolled blood pressure (BP) despite three or more antihypertensives, posing a high cardiovascular risk.
  • The endothelin pathway is implicated in RH, but endothelin antagonists have had limited clinical use.
  • Aprocitentan, a novel dual endothelin receptor antagonist, was recently FDA-approved for RH treatment.

Purpose of the Study:

  • To review the discovery, chemistry, pharmacokinetics, pharmacodynamics, efficacy, and safety of aprocitentan for resistant hypertension.
  • To summarize evidence on aprocitentan's role in pharmacotherapy for challenging hypertension cases.

Main Methods:

  • Review of preclinical studies and the landmark PRECISION trial data.
  • Analysis of aprocitentan's mechanism as an endothelin-1 (ET-1) receptor antagonist (ETA and ETB).

Main Results:

  • Aprocitentan demonstrated significant BP lowering in the PRECISION trial for resistant hypertension.
  • Efficacy was notable in elderly patients (>75 years), those with high cardiovascular risk, diabetes, and advanced chronic kidney disease (CKD).
  • Dual antagonism resulted in a lower risk of fluid retention and vascular leakage compared to other endothelin antagonists.

Conclusions:

  • Aprocitentan's novel mechanism, efficacy, and tolerability make it a promising option for resistant hypertension.
  • It may be particularly beneficial for patients with comorbidities like diabetes and CKD.