Document Detail


Vascular endothelin in hypertension.
MedLine Citation:
PMID:  15955745     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Endothelins are powerful vasoconstrictor peptides that also play numerous other functions in many different organs. Endothelin-1 (ET-1) is the most abundant and important of this family of peptides in blood vessels. Production of ET-1 is increased in the endothelium and the kidney in salt-dependent models of hypertension (e.g.: DOCA-salt rats and Dahl salt-sensitive rats, in salt-loaded SHR-SP, in angiotensin II-infused and in diabetic rats). ET-1 elicits an inflammatory response by increasing oxidant stress in the vascular wall, which induces vascular remodeling and endothelial dysfunction found in the hypertensive models that exhibit an endothelin-mediated component. Endothelin receptor antagonism reduces blood pressure and vascular hypertrophic remodeling present in these hypertensive models. Patients with stage 2 hypertension have enhanced vascular expression of ET-1. Endothelin receptor antagonists lower blood pressure in hypertensive patients. They could become therapeutic agents for prevention of target organ damage in hypertension and in type 2 diabetes, chronic renal failure and congestive heart failure. Side effects of endothelin receptor blockers have prevented up to the present their development for these indications. New endothelin antagonists devoid of these side effects, or alternatively inhibitors of the endothelin converting enzymes that generate ET-1 may in the future become available to block the endothelin system. However, to date endothelin antagonists have been approved only for the treatment of primary pulmonary hypertension, a rapidly fatal condition in which the endothelin system plays an important role and endothelin antagonists exert favorable effects.
Authors:
Ernesto L Schiffrin
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Review    
Journal Detail:
Title:  Vascular pharmacology     Volume:  43     ISSN:  1537-1891     ISO Abbreviation:  Vascul. Pharmacol.     Publication Date:  2005 Jun 
Date Detail:
Created Date:  2005-06-24     Completed Date:  2005-09-08     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  101130615     Medline TA:  Vascul Pharmacol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  19-29     Citation Subset:  IM    
Affiliation:
CIHR Multidisciplinary Research Group on Hypertension, Clinical Research Institute of Montreal, 110 Pine Avenue West, Montreal, Quebec H2W 1R7, Canada. ernesto.schiffrin@ircm.qc.ca
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MeSH Terms
Descriptor/Qualifier:
Amino Acid Sequence
Animals
Blood Vessels / drug effects,  metabolism,  physiopathology*
Endothelins / metabolism,  pharmacology,  physiology*
Humans
Hypertension / metabolism,  physiopathology*
Molecular Sequence Data
Muscle, Smooth, Vascular / drug effects
Chemical
Reg. No./Substance:
0/Endothelins

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


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