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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
6654
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pubmed:dateCreated |
1997-11-21
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pubmed:abstractText |
Abnormal smooth-muscle contractility may be a major cause of disease states such as hypertension, and a smooth-muscle relaxant that modulates this process would be useful therapeutically. Smooth-muscle contraction is regulated by the cytosolic Ca2+ concentration and by the Ca2+ sensitivity of myofilaments: the former activates myosin light-chain kinase and the latter is achieved partly by inhibition of myosin phosphatase. The small GTPase Rho and its target, Rho-associated kinase, participate in this latter mechanism in vitro, but their participation has not been demonstrated in intact muscles. Here we show that a pyridine derivative, Y-27632, selectively inhibits smooth-muscle contraction by inhibiting Ca2+ sensitization. We identified the Y-27632 target as a Rho-associated protein kinase, p160ROCK. Y-27632 consistently suppresses Rho-induced, p160ROCK-mediated formation of stress fibres in cultured cells and dramatically corrects hypertension in several hypertensive rat models. Our findings indicate that p160ROCK-mediated Ca2+ sensitization is involved in the pathophysiology of hypertension and suggest that compounds that inhibit this process might be useful therapeutically.
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pubmed:commentsCorrections |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Oct
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pubmed:issn |
0028-0836
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pubmed:author |
pubmed-author:InuiJJ,
pubmed-author:IshizakiTT,
pubmed-author:KawaharaTT,
pubmed-author:MaekawaMM,
pubmed-author:MorishitaTT,
pubmed-author:NarumiyaSS,
pubmed-author:OnoTT,
pubmed-author:SatohHH,
pubmed-author:TamakawaHH,
pubmed-author:UehataMM,
pubmed-author:YamagamiKK
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pubmed:issnType |
Print
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pubmed:day |
30
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pubmed:volume |
389
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
990-4
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pubmed:dateRevised |
2007-11-15
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pubmed:meshHeading |
pubmed-meshheading:9353125-Amides,
pubmed-meshheading:9353125-Animals,
pubmed-meshheading:9353125-Antihypertensive Agents,
pubmed-meshheading:9353125-COS Cells,
pubmed-meshheading:9353125-Calcium,
pubmed-meshheading:9353125-Cell Adhesion,
pubmed-meshheading:9353125-Enzyme Inhibitors,
pubmed-meshheading:9353125-Guinea Pigs,
pubmed-meshheading:9353125-Humans,
pubmed-meshheading:9353125-Hypertension,
pubmed-meshheading:9353125-Intracellular Signaling Peptides and Proteins,
pubmed-meshheading:9353125-Male,
pubmed-meshheading:9353125-Muscle, Smooth, Vascular,
pubmed-meshheading:9353125-Muscle Contraction,
pubmed-meshheading:9353125-Protein-Serine-Threonine Kinases,
pubmed-meshheading:9353125-Pyridines,
pubmed-meshheading:9353125-Rabbits,
pubmed-meshheading:9353125-Radioligand Assay,
pubmed-meshheading:9353125-Rats,
pubmed-meshheading:9353125-Rats, Wistar,
pubmed-meshheading:9353125-Recombinant Proteins,
pubmed-meshheading:9353125-Swine,
pubmed-meshheading:9353125-rho-Associated Kinases
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pubmed:year |
1997
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pubmed:articleTitle |
Calcium sensitization of smooth muscle mediated by a Rho-associated protein kinase in hypertension.
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pubmed:affiliation |
Discovery Research (Tokyo), Yoshitomi Pharmaceutical Industries Ltd, Saitama, Japan. uehata@yoshitomi.co.jp
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pubmed:publicationType |
Journal Article,
In Vitro,
Research Support, Non-U.S. Gov't
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