Endothelin-1 and endothelin receptor antagonists as potential cardiovascular therapeutic agents

Adviye Ergul

Research output: Contribution to journalReview article

41 Citations (Scopus)

Abstract

Endothelin (ET)-1 is an endothelium-derived peptide with potent vasoconstrictor and proliferative properties. The ET system is activated in several cardiovascular disease states associated with functional and structural vascular changes, including hypertension and heart failure. The two ET receptor subtypes are known as ETAR and ETBR. The former is located mainly on vascular smooth muscle cells and is responsible for mediating vasoconstriction and proliferation. The latter is present predominantly on endothelial cells and mediates vasorelaxation as well as ET-1 clearance. Activation of smooth muscle ETBR causes vasoconstriction. Selective ETAR antagonists as well as nonselective ETAR-ETBR antagonists have been developed. Studies with animal models and early-phase clinical trials provided strong evidence that these agents are effective in the treatment of heart failure, essential hypertension, pulmonary hypertension, and atherosclerosis. However, the complexity of biologic effects mediated by two different receptor subtypes complicates therapy with selective versus nonselective ET receptor antagonists. In addition to subtype selectivity and potency, changes in receptor subtype distribution under different pathologic conditions and different patient populations will play a crucial role in the evaluation of these potentially therapeutic drugs.

Original languageEnglish (US)
Pages (from-to)54-65
Number of pages12
JournalPharmacotherapy
Volume22
Issue number1 I
DOIs
StatePublished - Jan 16 2002

Fingerprint

Endothelin A Receptors
Cardiovascular Agents
Endothelin-1
Vasoconstriction
Heart Failure
Endothelin Receptors
Endothelins
Vasoconstrictor Agents
Treatment Failure
Vascular Smooth Muscle
Pulmonary Hypertension
Vasodilation
Smooth Muscle Myocytes
Endothelium
Smooth Muscle
Blood Vessels
Atherosclerosis
Cardiovascular Diseases
Endothelial Cells
Animal Models

ASJC Scopus subject areas

  • Pharmacology (medical)

Cite this

Endothelin-1 and endothelin receptor antagonists as potential cardiovascular therapeutic agents. / Ergul, Adviye.

In: Pharmacotherapy, Vol. 22, No. 1 I, 16.01.2002, p. 54-65.

Research output: Contribution to journalReview article

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