Importance of Subtype Selectivity for Endothelin Receptor Antagonists in the Human Vasculature



ET-1 acts via two receptors ETA and ETB. Many of the detrimental actions of ET-1 are mediated by ETA which predominates in smooth muscle of human vessels to cause vasoconstriction. Beneficial actions mediated by ETB include vasodilatation, clearing ET from the circulation, and promoting diuresis and natriuresis. Two classes of endothelin antagonist are currently in clinical use: ETA-selective and mixed antagonists that block both receptors. While ET antagonists have become established in the treatment of pulmonary arterial hypertension, the relative merit of the two classes continues to be debated. In order to classify antagonists as selective or mixed, it is important to have standardized measures of selectivity. This review compares endothelin receptor antagonist selectivity for compounds from different chemical classes measured in pharmacological assays using human tissue.


Pulmonary Arterial Hypertension Receptor Subtype Human Cardiovascular System Plasma Atrial Natriuretic Peptide Level Human Left Ventricle 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



We thank Dr. Neil Davie for discussion, Mrs. Rhoda Kuc for critically reading the manuscript, and the British Heart Foundation (grant numbers PG/09/050/27734 and RG/10/077/28300) and an investigator initiated grant from Pfizer for support.


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© Springer-Verlag London Limited 2012

Authors and Affiliations

  1. 1.University of Cambridge, Centre for Clinical Investigation, Addenbrooke’s HospitalCambridgeUK
  2. 2.Clinical Pharmacology UnitUniversity of Cambridge, Centre for Clinical Investigation, Addenbrooke’s HospitalCambridgeUK

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