Linked Life Data

15020300

Source:http://linkedlifedata.com/resource/pubmed/id/15020300

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2004-3-15
pubmed:abstractText
Endothelin-1 (ET-1) has acute positive inotropic effects, but consequences of chronically increased ET-1 on contractile function of cardiac myocytes are largely unknown. In the present study, effects of long-term treatment with ET-1 (10 nM) for 5 days on both force development [force of contraction (FOC)] and kinetics of contraction were determined in heart tissue reconstituted from rat cardiac cells. Isometric force was measured in response to cumulative concentrations of Ca(2+) and isoprenaline. ET-1 augmented basal FOC by 64 +/- 11% (P < 0.05), which was associated with a significantly blunted contractile response to Ca(2+) and isoprenaline. Moreover, ET-1 significantly prolonged relaxation (62 +/- 3 vs. 53 +/- 2 ms). Selective ET(A) (BQ-123) and ET(B) receptor blockade (BQ-788) demonstrated that effects of ET-1 on contractile function were mediated through the ET(A) receptor subtype. Effects of ET-1 were prevented by cotreatment with either Ro31-8425, a PKC inhibitor, or dimethylamiloride, an inhibitor of the Na(+)/H(+) exchanger. In contrast to long-term ET-1 treatment, no changes in contractile parameters were observed after ET-1 treatment for 3 h before force measurement. These data suggest that chronic ET-1 stimulation has dual effects on contractility: improvement of basal force but impairment of twitch kinetics and inotropic responsiveness to beta-adrenoceptor stimulation. The signaling pathways involved include ET(A) receptors, PKC, and the Na(+)/H(+) exchanger. The present in vitro findings raise the possibility that ET-1 may exert both adaptive and maladaptive effects in the failing myocardium in which local accumulation of ET-1 is present.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0363-6135
pubmed:author
pubmed:issnType
Print
pubmed:volume
286
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
H1248-57
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed-meshheading:15020300-Animals, pubmed-meshheading:15020300-Animals, Newborn, pubmed-meshheading:15020300-Endothelin-1, pubmed-meshheading:15020300-Enzyme Inhibitors, pubmed-meshheading:15020300-Fluorescent Antibody Technique, pubmed-meshheading:15020300-Gene Expression Regulation, pubmed-meshheading:15020300-Heart Ventricles, pubmed-meshheading:15020300-Hemodynamics, pubmed-meshheading:15020300-Humans, pubmed-meshheading:15020300-Isometric Contraction, pubmed-meshheading:15020300-Kinetics, pubmed-meshheading:15020300-Myocardial Contraction, pubmed-meshheading:15020300-Myocytes, Cardiac, pubmed-meshheading:15020300-Phenylalanine, pubmed-meshheading:15020300-Protein Kinase C, pubmed-meshheading:15020300-Rats, pubmed-meshheading:15020300-Rats, Wistar, pubmed-meshheading:15020300-Receptor, Endothelin A, pubmed-meshheading:15020300-Receptor, Endothelin B, pubmed-meshheading:15020300-Recombinant Proteins, pubmed-meshheading:15020300-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:15020300-Signal Transduction, pubmed-meshheading:15020300-Sodium-Hydrogen Antiporter
pubmed:year
2004
pubmed:articleTitle
Effects of chronic endothelin-1 stimulation on cardiac myocyte contractile function.
pubmed:affiliation
Institut für Experimentelle und Klinische Pharmakologie und Toxikologie, Friedrich-Alexander-Universität Erlangen-Nürnberg, 91054 Erlangen, Germany. Zolk@pharmakologie.uni-erlangen.de
pubmed:publicationType
Journal Article, In Vitro, Research Support, Non-U.S. Gov't