Document Detail


Endothelin receptor antagonists: clinical realities and future directions.
MedLine Citation:
PMID:  15654268     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Endothelin (ET) is among the strongest endogenous vasoconstrictors known and a potent mitogen. A rich body of experimental evidence suggests that ET contributes to vascular remodeling and end-organ damage in several cardiovascular conditions. Therefore, blockade of ET receptors has been suggested as an attractive target in a number of acute and chronic cardiovascular indications, including pulmonary arterial hypertension (PAH), systemic hypertension, and heart failure. To date, clinical studies have confirmed expectations in PAH and yielded promising initial results in systemic hypertension, which are currently awaiting confirmation in large-scale trials. In contrast, no added benefit could be demonstrated in large clinical trials on top of current standard treatment in both acute and chronic heart failure. Further clinical development in heart failure has therefore been suspended. Other indications that are currently being studied clinically or would possibly merit clinical trials include acute myocardial ischemia and reperfusion, cerebral vasospasm after intracranial bleeding, glaucoma, acute severe pancreatitis, systemic sclerosis, (diabetic) renal failure, restenosis after angioplasty/stent implantation, and late transplant rejection. This article critically reviews the available clinical data on ET receptor antagonism in cardiovascular indications against the background of the underlying preclinical research.
Authors:
Michael Kirchengast; Matthias Luz
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Publication Detail:
Type:  Journal Article; Review    
Journal Detail:
Title:  Journal of cardiovascular pharmacology     Volume:  45     ISSN:  0160-2446     ISO Abbreviation:  J. Cardiovasc. Pharmacol.     Publication Date:  2005 Feb 
Date Detail:
Created Date:  2005-01-17     Completed Date:  2005-05-03     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  7902492     Medline TA:  J Cardiovasc Pharmacol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  182-91     Citation Subset:  IM    
Affiliation:
Global Product Development Services, PRA International, Mannheim, Germany. kirchengastmichael@praintl.com
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MeSH Terms
Descriptor/Qualifier:
Animals
Cardiovascular Agents / pharmacology*,  therapeutic use*
Cardiovascular Diseases / drug therapy*,  physiopathology
Heart Failure / drug therapy,  physiopathology
Hemodynamics / drug effects
Humans
Hypertension / drug therapy
Hypertension, Pulmonary / drug therapy
Receptors, Endothelin / antagonists & inhibitors*
Ventricular Remodeling
Chemical
Reg. No./Substance:
0/Cardiovascular Agents; 0/Receptors, Endothelin

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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