Linked Life Data

12241541

Source:http://linkedlifedata.com/resource/pubmed/id/12241541

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2002-9-20
pubmed:abstractText
Increased circulating concentrations of tumour necrosis factor-alpha (TNF-alpha) are seen in several pathological conditions associated with vascular disease. TNF-alpha induces the synthesis of endothelin-1 (ET-1), a potent vasoconstictor, by the endothelium. However, there is profound vasodilatation in sepsis, where circulating levels of both ET-1 and TNF-alpha are elevated. The details of the interaction between ET-1 and TNF-alpha and the predominant resulting haemodynamic effect in healthy humans are unclear. The aim of the present study was to determine the effects of intra-arterial TNF-alpha on ET-1 spillover, vascular tone and endothelial function in the healthy human forearm. Brachial arterial and deep venous blood samples, forearm plasma flow measurements and blood flow responses to acetylcholine and sodium nitroprusside were obtained in six healthy subjects before and during a 6 h infusion of TNF-alpha into the brachial artery. Forearm blood flow was significantly greater than baseline during exposure to TNF-alpha [median (lower quartile, upper quartile): baseline, 2.6 (2.1, 2.8) ml.min(-1).100 ml(-1); TNF-alpha, 4.6 (4.5, 5.1) ml.min(-1).100 ml(-1); P <0.05]. The rate of release of ET-1 was significantly greater than baseline after 30 and 260 min of TNF-alpha infusion [median (lower quartile, upper quartile): baseline, 0.8 (0.6, 1.1) pg.min(-1).100 ml(-1); 30 min, 2.4 (1.9, 3.2) pg.min(-1).100 ml(-1); 260 min, 4.1 (3.1, 4.2) pg.min(-1).100 ml(-1); P <0.05]. The vasodilatory response to acetylcholine was diminished during TNF-alpha infusion, whereas the response to sodium nitroprusside remained unchanged. We thus demonstrate for the first time that local TNF-alpha increases ET-1 spillover from the human forearm and impairs endothelium-dependent vasodilatation. In spite of this action, TNF-alpha has a vasodilatory effect, resulting in an increase in forearm blood flow.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0143-5221
pubmed:author
pubmed:issnType
Print
pubmed:volume
103
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
409-15
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2002
pubmed:articleTitle
Effects of tumour necrosis factor-alpha in the human forearm: blood flow and endothelin-1 release.
pubmed:affiliation
Department of Medicine, Royal Free and University College London School of Medicine, Whittington Campus, London N19 3UA, UK. jnpatel104@aol.com
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't