Faculty Collaboration Database

Role of endothelin in cardiovascular disease. J Renin Angiotensin Aldosterone Syst 2002 Mar;3(1):1-15

Date

05/02/2002

Pubmed ID

11984741

DOI

10.3317/jraas.2002.001

Scopus ID

2-s2.0-0036004052 (requires institutional sign-in at Scopus site)   143 Citations

Abstract

Endothelins are a family of peptides, which comprises endothelin-1 (ET-1), endothelin-2 (ET-2) and endothelin-3 (ET-3), each containing 21 amino-acids. ET-1 is a peptide secreted mostly by vascular endothelial cells, the predominant isoform expressed in vasculature and the most potent vasoconstrictor currently known. ET-1 also has inotropic, chemotactic and mitogenic properties. In addition, it influences salt and water homeostasis through its effects on the renin-angiotensin-aldosterone system (RAAS), vasopressin and atrial natriuretic peptide and stimulates the sympathetic nervous system. The overall action of endothelin is to increase blood pressure and vascular tone. Therefore, endothelin antagonists may play an important role in the treatment of cardiac, vascular and renal diseases associated with regional or systemic vasoconstriction and cell proliferation, such as essential hypertension, pulmonary hypertension, chronic heart failure and chronic renal failure. Long-term anti-endothelin therapy may improve symptoms and favourably alter the progression of heart failure. Endothelin appears to participate in induction and progression of sclerotic renal changes, leading to progression to end-stage renal disease. Anti-endothelin therapy might offer additional benefits in the prevention of progression of chronic renal failure in addition to the known benefits of RAAS inhibition. Clinical trials have demonstrated potentially important benefits of endothelin antagonists for patients with essential hypertension, pulmonary hypertension and heart failure. Further studies are necessary to determine the role of anti-endothelin therapy in the treatment of cardiovascular diseases and determine the different roles of selective receptor antagonism vs. mixed ET(A/B)-receptor antagonism in human diseases.

Author List

Agapitov AV, Haynes WG

Author

Alexei V. Agapitov MD Staff Physician in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Amino Acid Sequence
Animals
Antihypertensive Agents
Arteriosclerosis
Cardiovascular Diseases
Endothelins
Heart Diseases
Hemodynamics
Humans
Hypertension
Kidney Failure, Chronic
Molecular Sequence Data
Signal Transduction