File Download
  Links for fulltext
     (May Require Subscription)
Supplementary

Article: Rho kinase inhibitors prevent endothelium-dependent contractions in the Rat Aorta

TitleRho kinase inhibitors prevent endothelium-dependent contractions in the Rat Aorta
Authors
Issue Date2009
PublisherAmerican Society for Pharmacology and Experimental Therapeutics. The Journal's web site is located at http://jpet.aspetjournals.org
Citation
Journal of Pharmacology And Experimental Therapeutics, 2009, v. 329 n. 2, p. 820-826 How to Cite?
AbstractRho kinase is involved in the pathogenesis of hypertension, which favors the occurrence of endothelium-dependent contractions. The present study was designed to determine the effects of two Rho kinase inhibitors, HA1077 [1-(5-isoquinoline-sulfonyl)-homopiperazine (fasudil)] and Y27632 [(+)-(R]-trans-4-(1-aminoethyl)-N-(4-pyridyl) cyclohexane carboxamide dihy-drochloride], on endothelium-dependent and -independent contractions. Isometric tension of 1-year-old spontaneously hypertensive rat and Wistar Kyoto aortae were measured. In the presence of Nω-nitro-L-arginine methyl ester, HA1077, and Y27632 reduced endothelium-dependent contractions caused by acetylcholine and the calcium ionophore 5-(methylamino)2-[[2R,3R,6S,8S,9R,11R)- 3,9,11-trimethyl-8-[(1S)-1-methyl-2- oxo-2-(1H-pyrrol-2-yl)-ethyl]-1,7- dioxaspiro[5.5]undec-2-yl]methyl]-4-benzoxazolecarboxylic acid (A23187). The Rho kinase inhibitors did not significantly affect prostacyclin production measured as 6-keto prostaglandin F1α,. They nearly abolished endothelium-independent contractions to (5Z)-7-[(1R,4S,5S,6R)-6-[(1E,3S)-3- hydroxy-1-octenyl]-2-oxabicyclo-[2.2.1]hept-5-yl]-5-heptenoic acid (U46619), prostaglandin F2α, and phenylephrine. Western blotting revealed a comparable expression of Rho kinase in the aortae of the two strains. The reduction by Rho kinase inhibitors of endothelium-dependent contractions is mainly because of their direct effect on the vascular smooth muscle cells. Copyright © 2009 by The American Society for Pharmacology and Experimental Therapeutics.
Persistent Identifierhttp://hdl.handle.net/10722/59230
ISSN
2015 Impact Factor: 3.76
2015 SCImago Journal Rankings: 1.847
ISI Accession Number ID
Funding AgencyGrant Number
Research Grant Council of Hong Kong
Research Centre of Heart, Brain, Hormone and Healthy Aging, University of Hong Kong777507M
Funding Information:

This work was supported by the Research Grant Council of Hong Kong and the Research Centre of Heart, Brain, Hormone and Healthy Aging [ Grant University of Hong Kong-777507M].

References

 

DC FieldValueLanguage
dc.contributor.authorChan, CKYen_HK
dc.contributor.authorMak, JCen_HK
dc.contributor.authorMan, RYKen_HK
dc.contributor.authorVanhoutte, PMen_HK
dc.date.accessioned2010-05-31T03:45:42Z-
dc.date.available2010-05-31T03:45:42Z-
dc.date.issued2009en_HK
dc.identifier.citationJournal of Pharmacology And Experimental Therapeutics, 2009, v. 329 n. 2, p. 820-826en_HK
dc.identifier.issn0022-3565en_HK
dc.identifier.urihttp://hdl.handle.net/10722/59230-
dc.description.abstractRho kinase is involved in the pathogenesis of hypertension, which favors the occurrence of endothelium-dependent contractions. The present study was designed to determine the effects of two Rho kinase inhibitors, HA1077 [1-(5-isoquinoline-sulfonyl)-homopiperazine (fasudil)] and Y27632 [(+)-(R]-trans-4-(1-aminoethyl)-N-(4-pyridyl) cyclohexane carboxamide dihy-drochloride], on endothelium-dependent and -independent contractions. Isometric tension of 1-year-old spontaneously hypertensive rat and Wistar Kyoto aortae were measured. In the presence of Nω-nitro-L-arginine methyl ester, HA1077, and Y27632 reduced endothelium-dependent contractions caused by acetylcholine and the calcium ionophore 5-(methylamino)2-[[2R,3R,6S,8S,9R,11R)- 3,9,11-trimethyl-8-[(1S)-1-methyl-2- oxo-2-(1H-pyrrol-2-yl)-ethyl]-1,7- dioxaspiro[5.5]undec-2-yl]methyl]-4-benzoxazolecarboxylic acid (A23187). The Rho kinase inhibitors did not significantly affect prostacyclin production measured as 6-keto prostaglandin F1α,. They nearly abolished endothelium-independent contractions to (5Z)-7-[(1R,4S,5S,6R)-6-[(1E,3S)-3- hydroxy-1-octenyl]-2-oxabicyclo-[2.2.1]hept-5-yl]-5-heptenoic acid (U46619), prostaglandin F2α, and phenylephrine. Western blotting revealed a comparable expression of Rho kinase in the aortae of the two strains. The reduction by Rho kinase inhibitors of endothelium-dependent contractions is mainly because of their direct effect on the vascular smooth muscle cells. Copyright © 2009 by The American Society for Pharmacology and Experimental Therapeutics.en_HK
dc.languageengen_HK
dc.publisherAmerican Society for Pharmacology and Experimental Therapeutics. The Journal's web site is located at http://jpet.aspetjournals.orgen_HK
dc.relation.ispartofJournal of Pharmacology and Experimental Therapeuticsen_HK
dc.subject.mesh1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine - analogs & derivatives - chemistry - pharmacologyen_HK
dc.subject.meshAmides - chemistry - pharmacologyen_HK
dc.subject.meshAnimalsen_HK
dc.subject.meshAntihypertensive Agents - chemistry - pharmacologyen_HK
dc.subject.meshAorta, Thoracic - drug effects - enzymology - physiopathologyen_HK
dc.subject.meshBlotting, Westernen_HK
dc.subject.meshDose-Response Relationship, Drugen_HK
dc.subject.meshEndothelium, Vascular - drug effects - enzymology - physiologyen_HK
dc.subject.meshHypertension - drug therapy - enzymology - physiopathologyen_HK
dc.subject.meshIsometric Contraction - drug effectsen_HK
dc.subject.meshMaleen_HK
dc.subject.meshPyridines - chemistry - pharmacologyen_HK
dc.subject.meshRatsen_HK
dc.subject.meshRats, Inbred SHRen_HK
dc.subject.meshRats, Inbred WKYen_HK
dc.subject.meshSpecies Specificityen_HK
dc.subject.meshVasoconstriction - drug effectsen_HK
dc.subject.meshrho-Associated Kinases - antagonists & inhibitors - biosynthesisen_HK
dc.titleRho kinase inhibitors prevent endothelium-dependent contractions in the Rat Aortaen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0022-3565&volume=329&spage=820&epage=826&date=2009&atitle=Rho+kinase+inhibitors+prevent+endothelium-dependent+contractions+in+the+rat+aortaen_HK
dc.identifier.emailMak, JC: judymak@hku.hken_HK
dc.identifier.emailMan, RYK: rykman@hkucc.hku.hken_HK
dc.identifier.emailVanhoutte, PM: vanhoutt@hku.hken_HK
dc.identifier.authorityMak, JC=rp00352en_HK
dc.identifier.authorityMan, RYK=rp00236en_HK
dc.identifier.authorityVanhoutte, PM=rp00238en_HK
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1124/jpet.108.148247en_HK
dc.identifier.pmid19193928-
dc.identifier.scopuseid_2-s2.0-65649115407en_HK
dc.identifier.hkuros157370en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-65649115407&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume329en_HK
dc.identifier.issue2en_HK
dc.identifier.spage820en_HK
dc.identifier.epage826en_HK
dc.identifier.isiWOS:000265444000045-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridChan, CKY=35209921200en_HK
dc.identifier.scopusauthoridMak, JC=7103323094en_HK
dc.identifier.scopusauthoridMan, RYK=7004986435en_HK
dc.identifier.scopusauthoridVanhoutte, PM=7202304247en_HK
dc.identifier.citeulike8153556-
dc.customcontrol.immutablesml 140808-

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats