Linked Life Data

12970111

Source:http://linkedlifedata.com/resource/pubmed/id/12970111

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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8
pubmed:dateCreated
2003-10-17
pubmed:abstractText
Sympathomimetic stimulation, angiotensin II, or endothelin-1 is considered to be an essential stimulus mediating ventricular hypertrophy. Adenosine is known to protect the heart from excessive catecholamine exposure, reduce production of endothelin-1, and attenuate the activation of the renin-angiotensin system. These findings suggest that adenosine may also attenuate myocardial hypertrophy. To verify this hypothesis, we examined whether activation of adenosine receptors can attenuate cardiac hypertrophy and reduce the risk of heart failure. Our in vitro study of neonatal rat cardiomyocytes showed that 2-chloroadenosine (CADO), a stable adenosine analogue, inhibits protein synthesis of cardiomyocytes induced by phenylephrine, endothelin-1, angiotensin II, or isoproterenol, which were mimicked by the stimulation of adenosine A1 receptors. For our in vivo study, cardiac hypertrophy was induced by transverse aortic constriction (TAC) in C57BL/6 male mice. Four weeks after TAC, both heart to body weight ratio (6.80+/-0.18 versus 8.34+/-0.33 mg/g, P<0.0001) as well as lung to body weight ratio (6.23+/-0.27 versus 10.03+/-0.85 mg/g, P<0.0001) became significantly lower in CADO-treated mice than in the TAC group. Left ventricular fractional shortening and left ventricular dP/dtmax were improved significantly by CADO treatment. Similar results were obtained using the selective adenosine A1 agonist N6-cyclopentyladenosine (CPA). A nonselective adenosine antagonist, 8-(p-sulfophenyl)-theophylline, and a selective adenosine A1 antagonist, 8-cyclopentyl-1,3-dipropylxanthine, eliminated the antihypertrophic effect of CADO and CPA, respectively. The plasma norepinephrine level was decreased and myocardial expression of regulator of G protein signaling 4 was upregulated in CADO-treated mice. These results indicate that the stimulation of adenosine receptors attenuates both the cardiac hypertrophy and myocardial dysfunction via adenosine A1 receptor-mediated mechanisms.
pubmed:commentsCorrections
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
1524-4571
pubmed:author
pubmed:issnType
Electronic
pubmed:day
17
pubmed:volume
93
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
759-66
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed-meshheading:12970111-2-Chloroadenosine, pubmed-meshheading:12970111-Animals, pubmed-meshheading:12970111-Aorta, pubmed-meshheading:12970111-Cells, Cultured, pubmed-meshheading:12970111-Constriction, pubmed-meshheading:12970111-Cyclic AMP-Dependent Protein Kinases, pubmed-meshheading:12970111-Heart Failure, pubmed-meshheading:12970111-Heterotrimeric GTP-Binding Proteins, pubmed-meshheading:12970111-Hypertrophy, Left Ventricular, pubmed-meshheading:12970111-Male, pubmed-meshheading:12970111-Mice, pubmed-meshheading:12970111-Mice, Inbred C57BL, pubmed-meshheading:12970111-Myocytes, Cardiac, pubmed-meshheading:12970111-Purinergic P1 Receptor Agonists, pubmed-meshheading:12970111-Purinergic P1 Receptor Antagonists, pubmed-meshheading:12970111-Receptors, Cell Surface, pubmed-meshheading:12970111-Ventricular Pressure
pubmed:year
2003
pubmed:articleTitle
Activation of adenosine A1 receptor attenuates cardiac hypertrophy and prevents heart failure in murine left ventricular pressure-overload model.
pubmed:affiliation
Department of Internal Medicine and Therapeutics, Osaka University Graduate School of Medicine, Osaka, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't