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Predicate | Object |
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rdf:type | |
lifeskim:mentions |
umls-concept:C0020542,
umls-concept:C0034715,
umls-concept:C0079284,
umls-concept:C0205177,
umls-concept:C0205531,
umls-concept:C0226896,
umls-concept:C0231491,
umls-concept:C0387926,
umls-concept:C0442027,
umls-concept:C1292733,
umls-concept:C1527415,
umls-concept:C1555029,
umls-concept:C1801960,
umls-concept:C2709248
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pubmed:issue |
6
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pubmed:dateCreated |
1997-8-29
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pubmed:abstractText |
Exposure to hypoxia is associated with increased pulmonary artery pressure and plasma endothelin (ET-1) levels and with selective enhancement of ET-1 peptide and messenger RNA (mRNA) and endothelin-A (ET-A) receptor mRNA in rat lung. Our study tested the hypothesis that A-127722, an orally active antagonist of the ET-A receptor, can prevent hypoxia-induced pulmonary hypertension and vascular remodeling in the rat. Pretreatment with A-127722 (3, 10, and 30 mg/kg/day in drinking water for 2 days) caused dose-dependent inhibition of the pulmonary vasoconstrictor response to short-term hypoxia (10% O2, 90 min). Long-term A-127722 treatment (10 mg/kg/day in drinking water for 2 weeks) instituted 48 h before hypoxic exposure attenuated the subsequent development of pulmonary hypertension, the associated right atrial hypertrophy, and pulmonary vascular remodeling. Institution of A-127722 treatment (10 mg/kg/day in drinking water for 4 weeks) after 2 weeks of hypoxia retarded the progression of established hypoxia-induced pulmonary hypertension and right atrial hypertrophy and reversed the pulmonary vascular remodeling despite continuing hypoxic exposure. These findings support the hypothesis that endogenous ET-1 plays a major role in hypoxic pulmonary vasoconstriction/hypertension, right heart hypertrophy, and pulmonary vascular remodeling and suggest that ET-A receptor blockers may be useful in the treatment and prevention of hypoxic pulmonary hypertension in humans.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/A 127722,
http://linkedlifedata.com/resource/pubmed/chemical/Endothelin-1,
http://linkedlifedata.com/resource/pubmed/chemical/Pyrrolidines,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, Endothelin A,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Endothelin
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pubmed:status |
MEDLINE
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pubmed:month |
Jun
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pubmed:issn |
0160-2446
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
29
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
713-25
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pubmed:dateRevised |
2004-1-20
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pubmed:meshHeading |
pubmed-meshheading:9234651-Animals,
pubmed-meshheading:9234651-Anoxia,
pubmed-meshheading:9234651-Blood Pressure,
pubmed-meshheading:9234651-Cardiomegaly,
pubmed-meshheading:9234651-Endothelin-1,
pubmed-meshheading:9234651-Heart Rate,
pubmed-meshheading:9234651-Hypertension, Pulmonary,
pubmed-meshheading:9234651-Male,
pubmed-meshheading:9234651-Pulmonary Artery,
pubmed-meshheading:9234651-Pyrrolidines,
pubmed-meshheading:9234651-Rats,
pubmed-meshheading:9234651-Receptor, Endothelin A,
pubmed-meshheading:9234651-Receptors, Endothelin
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pubmed:year |
1997
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pubmed:articleTitle |
The orally active nonpeptide endothelin A-receptor antagonist A-127722 prevents and reverses hypoxia-induced pulmonary hypertension and pulmonary vascular remodeling in Sprague-Dawley rats.
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pubmed:affiliation |
Vascular Biology and Hypertension Program, Division of Cardiovascular Disease, University of Alabama at Birmingham, 35294-0007, USA.
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pubmed:publicationType |
Journal Article
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