Document Detail

The activation of endothelin-1 pathway during methionine-induced homocysteinemia mediates endothelial dysfunction in hypertensive individuals.
MedLine Citation:
PMID:  20160653     Owner:  NLM     Status:  MEDLINE    
OBJECTIVES: Endothelin-1 (ET-1) is a key regulator of arterial blood pressure in humans, and homocysteinemia is associated with increased oxidative stress. It is still unclear whether homocysteine-induced oxidative stress is implicated in the regulation of ET-1 expression. We examined the impact of acute homocysteinemia on endothelial function in hypertensive patients and healthy individuals, and the potential role of ET-1. METHODS: In this double-blind, placebo-controlled study, 39 hypertensive and 49 healthy individuals were randomized to receive high-dose vitamins (2 g vitamin C and 800IU vitamin E) or placebo followed by methionine loading 100 mg/kg body weight. Endothelium-dependent dilation (EDD) and endothelium-independent dilation (EID) of the brachial artery were evaluated by plethysmography, at baseline and 4 h postloading (4 h PML). ET-1 was measured by ELISA, whereas total lipid hydroperoxides (per-ox) levels were measured by a commercially available photometric technique. RESULTS: Acute, methionine-induced homocysteinemia decreased EDD in all study groups (P < 0.001 for all), whereas vitamins pretreatment failed to prevent this effect, despite the vitamins-induced reduction of peroxidation in the hypertensives group (P < 0.05). On the contrary, methionine loading significantly increased plasma ET-1 levels only in hypertensives (P < 0.05), an effect which was not prevented by antioxidant vitamins (P < 0.05). EID remained unchanged after methionine loading, in all study groups (P = NS for all groups). CONCLUSION: Experimental homocysteinemia rapidly blunts endothelial function in both hypertensive individuals and healthy individuals. The rapid elevation of ET-1 levels observed only in hypertensives, suggests that ET-1 may be the key mediator of homocysteine-induced endothelial dysfunction, independently of oxidative stress.
Dimitris Tousoulis; George Bouras; Charalambos Antoniades; Kyriakoula Marinou; Antigoni Miliou; Nikos Papageorgiou; George Chatzis; Costas Tentolouris; Costas Tsioufis; Christodoulos Stefanadis
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Publication Detail:
Type:  Journal Article; Randomized Controlled Trial    
Journal Detail:
Title:  Journal of hypertension     Volume:  28     ISSN:  1473-5598     ISO Abbreviation:  J. Hypertens.     Publication Date:  2010 May 
Date Detail:
Created Date:  2010-04-16     Completed Date:  2010-07-29     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8306882     Medline TA:  J Hypertens     Country:  England    
Other Details:
Languages:  eng     Pagination:  925-30     Citation Subset:  IM    
S Karagiorga 69, Glifada 166 75, Athens, Greece.
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MeSH Terms
Ascorbic Acid / administration & dosage
Double-Blind Method
Endothelin-1 / blood,  physiology*
Endothelium, Vascular / drug effects,  physiopathology
Homocysteine / blood*
Hyperhomocysteinemia / blood,  etiology,  physiopathology*
Hypertension / blood,  physiopathology*
Methionine / administration & dosage*
Oxidative Stress
Signal Transduction
Vasodilation / drug effects
Vitamin E / administration & dosage
Reg. No./Substance:
0/Endothelin-1; 1406-18-4/Vitamin E; 454-28-4/Homocysteine; 50-81-7/Ascorbic Acid; 63-68-3/Methionine

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

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