Source:http://linkedlifedata.com/resource/pubmed/id/17312448
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
2
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| pubmed:dateCreated |
2007-2-21
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| pubmed:abstractText |
Pulmonary arterial hypertension is a progressive and fatal disease for which Rho-kinase may be substantially involved. In this study, we examined the acute vasodilator effects of fasudil, a Rho-kinase inhibitor, in monocrotaline (MCT)-induced pulmonary hypertension (PH) in rats. Three weeks after a single subcutaneous injection of MCT (60 mg/kg), hemodynamic variables were measured under conscious and free-moving conditions before and after oral administration of fasudil. MCT caused a significant elevation of mean pulmonary arterial pressure (mPAP). Although a low dose of fasudil (3 mg/kg) had no effect on mPAP, a middle dose (10 mg/kg) caused a significant reduction in mPAP without change in mean systemic arterial pressure (mSAP), and a high dose (30 mg/kg) significantly reduced both mPAP and mSAP. Rho-kinase activity was significantly increased by MCT injection in pulmonary arteries but not in the aorta. Fasudil (10 mg/kg) inhibited only the Rho-kinase activity in pulmonary arteries without any effect in the aorta. Plasma concentration of hydroxyfasudil, a metabolite of fasudil, was within its clinical range in humans. These results demonstrate that fasudil exerts effective and selective vasodilatation of pulmonary arteries in rats with MCT-induced PH at a given dose, suggesting its usefulness for the treatment of the fatal disorder.
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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/1-(5-Isoquinolinesulfonyl)-2-Methylp...,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Intracellular Signaling Peptides...,
http://linkedlifedata.com/resource/pubmed/chemical/Monocrotaline,
http://linkedlifedata.com/resource/pubmed/chemical/Poisons,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/fasudil,
http://linkedlifedata.com/resource/pubmed/chemical/rho-Associated Kinases
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| pubmed:status |
MEDLINE
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| pubmed:month |
Feb
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| pubmed:issn |
0160-2446
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:volume |
49
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
85-9
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| pubmed:dateRevised |
2007-11-15
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| pubmed:meshHeading |
pubmed-meshheading:17312448-1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine,
pubmed-meshheading:17312448-Animals,
pubmed-meshheading:17312448-Blood Pressure,
pubmed-meshheading:17312448-Blotting, Western,
pubmed-meshheading:17312448-Dose-Response Relationship, Drug,
pubmed-meshheading:17312448-Enzyme Inhibitors,
pubmed-meshheading:17312448-Heart Rate,
pubmed-meshheading:17312448-Hypertension, Pulmonary,
pubmed-meshheading:17312448-Intracellular Signaling Peptides and Proteins,
pubmed-meshheading:17312448-Male,
pubmed-meshheading:17312448-Monocrotaline,
pubmed-meshheading:17312448-Poisons,
pubmed-meshheading:17312448-Protein-Serine-Threonine Kinases,
pubmed-meshheading:17312448-Pulmonary Artery,
pubmed-meshheading:17312448-Pulmonary Circulation,
pubmed-meshheading:17312448-Rats,
pubmed-meshheading:17312448-Rats, Sprague-Dawley,
pubmed-meshheading:17312448-Vasodilation,
pubmed-meshheading:17312448-rho-Associated Kinases
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| pubmed:year |
2007
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| pubmed:articleTitle |
Acute vasodilator effect of fasudil, a Rho-kinase inhibitor, in monocrotaline-induced pulmonary hypertension in rats.
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| pubmed:affiliation |
Department of Cardiovascular Medicine, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan.
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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