title: Endothelin ETA receptor antagonism in cardiovascular disease.
abstract: Since the discovery of the endothelin system in 1988, it has been implicated in numerous physiological and pathological phenomena. In the cardiovascular system, endothelin-1 (ET-1) acts through intracellular pathways of two endothelin receptors (ETA and ETB) located mainly on smooth muscle and endothelial cells to regulate vascular tone and provoke mitogenic and proinflammatory reactions. The endothelin ETA receptor is believed to play a pivotal role in the pathogenesis of several cardiovascular disease including systemic hypertension, pulmonary arterial hypertension (PAH), dilated cardiomyopathy, and diabetic microvascular dysfunction. Growing evidence from recent experimental and clinical studies indicates that the blockade of endothelin receptors, particularly the ETA subtype, grasps promise in the treatment of major cardiovascular pathologies. The simultaneous blockade of endothelin ETB receptors might not be advantageous, leading possibly to vasoconstriction and salt and water retentions. This review summarizes the role of ET-1 in cardiovascular modulation and the therapeutic potential of endothelin receptor antagonism.
authors: Department of Pharmacology, Faculty of Pharmacy, Beirut Arab University, Lebanon.
authors: Suzanne A
authors: SA
authors: Nasser
authors: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Alexandria University, Egypt. Electronic address: mahelm@hotmail.com.
authors: Mahmoud M
authors: MM
authors: El-Mas
mesh_terms: D000818:Animals; D002318:Cardiovascular Diseases / Q000188:drug therapy / Q000378:metabolism*; D065130:Endothelin A Receptor Antagonists / Q000494:pharmacology / Q000627:therapeutic use; D019332:Endothelin-1 / Q000378:metabolism; D006801:Humans; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D044022:Receptor, Endothelin A / Q000378:metabolism*
chemical_list: D065130:Endothelin A Receptor Antagonists; D019332:Endothelin-1; D044022:Receptor, Endothelin A
keywords: Cardiovascular disease; ET(A) receptor antagonists; Endothelin-1