| Cardiovascular effects of Y-27632, a selective Rho-associated kinase inhibitor, assessed in the halothane-anesthetized canine model. | |
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MedLine Citation:
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PMID: 12535859 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Y-27632, (+)-(R)-trans-4-(1-aminoethyl)-N-(4-pyridyl) cyclohexanecarboxamide dihydrochloride monohydrate, is a selective Rho-associated kinase inhibitor, which has been suggested to possess multiple clinical applications based on the in vitro observations. Since information regarding in vivo cardiovascular effects of Y-27632 is still limited, we assessed them using the halothane-anesthetized, closed-chest canine model. Administration of Y-27632 in a dose of 0.01 mg/kg, i.v. significantly decreased total peripheral vascular resistance together with an increase of cardiac output without affecting other cardiovascular parameters. Moreover, additional administration of Y-27632 in a dose of 0.1 mg/kg, i.v. significantly decreased blood pressure and left ventricular end-diastolic pressure, increased the heart rate and cardiac contractility, enhanced atrioventricular conduction and shortened the repolarization process as well as the effective refractory period. These results indicate that Y-27632 exerts a potent arterio-venodilator action with cardiostimulatory effects possibly through the sympathetic reflex in the in vivo canine model. |
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Authors:
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Akira Takahara; Atsushi Sugiyama; Yoshioki Satoh; Masahiko Yoneyama; Keitaro Hashimoto |
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Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: European journal of pharmacology Volume: 460 ISSN: 0014-2999 ISO Abbreviation: Eur. J. Pharmacol. Publication Date: 2003 Jan |
Date Detail:
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Created Date: 2003-01-21 Completed Date: 2003-08-04 Revised Date: 2007-11-15 |
Medline Journal Info:
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Nlm Unique ID: 1254354 Medline TA: Eur J Pharmacol Country: Netherlands |
Other Details:
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Languages: eng Pagination: 51-7 Citation Subset: IM |
Affiliation:
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Department of Pharmacology, University of Yamanashi Faculty of Medicine, Tamaho-cho, Nakakoma-gun, Yamanashi 409-3898, Japan. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Amides
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pharmacology* Anesthetics, Inhalation / pharmacology* Animals Blood Pressure / drug effects, physiology Cardiovascular System / drug effects*, enzymology Carrier Proteins / pharmacology Dogs Enzyme Inhibitors / pharmacology* Female Halothane / pharmacology* Heart Rate / drug effects, physiology Intracellular Signaling Peptides and Proteins* Protein-Serine-Threonine Kinases / antagonists & inhibitors*, metabolism Pyridines / pharmacology* rho-Associated Kinases |
| Chemical | |
Reg. No./Substance:
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0/Amides; 0/Anesthetics, Inhalation; 0/Carrier Proteins; 0/Enzyme Inhibitors; 0/Intracellular Signaling Peptides and Proteins; 0/Pyridines; 0/protein kinase modulator; 138381-45-0/Y 27632; 151-67-7/Halothane; EC 2.7.11.1/Protein-Serine-Threonine Kinases; EC 2.7.11.1/rho-Associated Kinases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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