Clinical Strategies For Managing Resistant Hypertension: Emerging Tools and Therapeutic Insights - Episode 5
Rationale for Targeting the Endothelin Pathway In RH
Panelists discuss how endothelin receptor antagonism addresses resistant hypertension by blocking one of the most potent vasoconstrictors, reducing smooth muscle hypertrophy and fibrosis, with aprocitentan being the only endothelin receptor antagonist approved for resistant hypertension.
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The endothelin pathway represents an innovative therapeutic target in resistant hypertension (RH) management, addressing a potent vasoconstrictor mechanism left unopposed by traditional ACD therapy. Endothelin-1 is one of the most powerful vasoconstrictors in the human body, causing arterial constriction, smooth muscle hypertrophy, reduced vascular compliance, and progressive fibrosis that contributes to both blood pressure elevation and target organ damage.
Aprocitentan represents the first endothelin receptor antagonist specifically approved for resistant hypertension treatment, offering a unique mechanism of action distinct from existing antihypertensive drug classes. Unlike other endothelin receptor antagonists like bosentan and macitentan (used for pulmonary hypertension), aprocitentan is specifically indicated for systemic hypertension and provides both renal and vascular benefits through dual endothelin receptor blockade.
The endothelin pathway’s role in resistant hypertension extends beyond simple vasoconstriction, contributing to microvascular dysfunction, inflammatory processes, and progressive vascular remodeling that perpetuates hypertension despite conventional treatment. By targeting this pathway, aprocitentan addresses fundamental pathophysiologic mechanisms underlying treatment resistance, offering hope for patients who remain uncontrolled despite optimal conventional therapy and providing clinicians with an additional tool in their therapeutic armamentarium.
