Document Detail

Endothelin in hypertension: an update.
MedLine Citation:
PMID:  22257795     Owner:  NLM     Status:  MEDLINE    
PURPOSE OF REVIEW: The purpose of this review of the vascular biology of endothelin-1 (ET-1) is the presentation of recent data including the use of endothelin-receptor antagonists for the treatment of hypertension.
RECENT FINDINGS: Recent discoveries regarding the pharmacology of ET-1 in the vascular wall and its effect on signalling transduction and gene expression in vascular smooth muscle cells are reviewed, as well as mechanisms controlling blood pressure in normal conditions and in hypertension, discovered using genetically modified models. Finally, studies of endothelin antagonists for treatment of hypertension will be summarized.
SUMMARY: Pharmacological studies demonstrate that calcitonin gene-related peptide is a physiological antagonist of ET-1 that terminates the long-lasting contraction induced by ET-1. ET-1-induced rise in [Ca]i involves the newly described stromal-interaction molecule-1/orai1 pathway to increase store-operated calcium entry. Sensitization of contractile proteins to calcium during ET-1-induced contraction of vascular smooth muscle cells includes activation of p63Rho guanine nucleotide exchange factor and increase in O-GlcNAcylation, a form of posttranslational modification. Genetically modified mice have demonstrated that endothelial ET-1 is involved in the regulation of normal blood pressure and development of vascular disease. Gene expression induced by endothelial overexpression of ET-1 in mice demonstrated upregulation of lipid metabolism, inflammatory and signal transduction genes. Crossing these mice with apoE mice was associated with acceleration of atherosclerosis on a high-fat diet and blood pressure elevation. Finally, the DORADO clinical trial has demonstrated that the ETA-receptor antagonist darusentan is able to decrease the blood pressure of patients with refractory hypertension.
Yohann Rautureau; Ernesto L Schiffrin
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Review    
Journal Detail:
Title:  Current opinion in nephrology and hypertension     Volume:  21     ISSN:  1473-6543     ISO Abbreviation:  Curr. Opin. Nephrol. Hypertens.     Publication Date:  2012 Mar 
Date Detail:
Created Date:  2012-02-08     Completed Date:  2012-06-04     Revised Date:  2013-05-02    
Medline Journal Info:
Nlm Unique ID:  9303753     Medline TA:  Curr Opin Nephrol Hypertens     Country:  England    
Other Details:
Languages:  eng     Pagination:  128-36     Citation Subset:  IM    
Lady Davis Institute for Medical Research, Sir Mortimer B. Davis-Jewish General Hospital, McGill University, Montréal, Québec, Canada.
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MeSH Terms
Atherosclerosis / metabolism,  physiopathology
Blood Pressure
Endothelin-1 / antagonists & inhibitors,  metabolism*
Gene Expression Regulation
Hypertension / drug therapy,  metabolism*,  physiopathology
Muscle, Smooth, Vascular / metabolism*,  physiopathology
Receptors, Endothelin / antagonists & inhibitors
Signal Transduction*
Grant Support
102606//Canadian Institutes of Health Research; 37917//Canadian Institutes of Health Research; 82790//Canadian Institutes of Health Research
Reg. No./Substance:
0/Endothelin-1; 0/Receptors, Endothelin

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

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