Document Detail


Cardiovascular effects of Y-27632, a selective Rho-associated kinase inhibitor, assessed in the halothane-anesthetized canine model.
MedLine Citation:
PMID:  12535859     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Akira Takahara; Atsushi Sugiyama; Yoshioki Satoh; Masahiko Yoneyama; Keitaro Hashimoto
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  European journal of pharmacology     Volume:  460     ISSN:  0014-2999     ISO Abbreviation:  Eur. J. Pharmacol.     Publication Date:  2003 Jan 
Date Detail:
Created Date:  2003-01-21     Completed Date:  2003-08-04     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  1254354     Medline TA:  Eur J Pharmacol     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  51-7     Citation Subset:  IM    
Affiliation:
Department of Pharmacology, University of Yamanashi Faculty of Medicine, Tamaho-cho, Nakakoma-gun, Yamanashi 409-3898, Japan.
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MeSH Terms
Descriptor/Qualifier:
Amides / 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:
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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