Document Detail


Effects of fasudil, a Rho-associated protein kinase inhibitor, on optic nerve head blood flow in rabbits.
MedLine Citation:
PMID:  20720232     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
PURPOSE: To investigate the effects of fasudil, a Rho-associated coiled coil-forming protein kinase (ROCK) inhibitor, on normal or impaired optic nerve head (ONH) blood flow in a rabbit model.
METHODS: ONH blood flow was measured by laser speckle flowgraphy. Changes in ONH blood flow were examined during a continuous intravenous infusion of fasudil with and without the application of N(G)-nitro-L-arginine methyl ester (L-NAME), a nitric oxide synthase inhibitor. Effects of topical fasudil on ONH blood flow were investigated in normal eyes or models of ocular circulation impairment induced by the application of endothelin (ET)-1. Visual-evoked potentials (VEPs) and morphologic and histologic changes were also analyzed in the ET-1-injected eyes.
RESULTS: A continuous intravenous infusion of fasudil had no significant effect on normal ONH blood flow, yet it prevented or improved the ONH blood flow impairment induced by the intravenous injection of L-NAME. Repeated intravitreal injections of ET-1 twice a week for 4 weeks decreased the ONH blood flow, prolonged the VEPs' implicit time, enlarged the optic cup, and decreased retinal ganglion cells. Multiple doses of topical fasudil ameliorated the ONH impairments caused by ET-1.
CONCLUSIONS: These results show that systemic or topical fasudil suppresses impairment of ONH blood flow, function, and morphology induced by L-NAME or ET-1. A ROCK inhibitor can be useful for the treatment of impaired ONH blood flow.
Authors:
Tetsuya Sugiyama; Maho Shibata; Sumiko Kajiura; Takashi Okuno; Masahiro Tonari; Hidehiro Oku; Tsunehiko Ikeda
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2011-01-05
Journal Detail:
Title:  Investigative ophthalmology & visual science     Volume:  52     ISSN:  1552-5783     ISO Abbreviation:  Invest. Ophthalmol. Vis. Sci.     Publication Date:  2011 Jan 
Date Detail:
Created Date:  2011-01-06     Completed Date:  2011-02-07     Revised Date:  2011-03-04    
Medline Journal Info:
Nlm Unique ID:  7703701     Medline TA:  Invest Ophthalmol Vis Sci     Country:  United States    
Other Details:
Languages:  eng     Pagination:  64-9     Citation Subset:  IM    
Affiliation:
Department of Ophthalmology, Osaka Medical College, Takatsuki, Osaka, Japan. tsugiyama@poh.osaka-med.ac.jp
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MeSH Terms
Descriptor/Qualifier:
1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / administration & dosage,  analogs & derivatives*
Administration, Topical
Animals
Blood Flow Velocity / drug effects
Blood Pressure / drug effects
Endothelin-1 / pharmacology
Evoked Potentials, Visual / drug effects
Infusions, Intravenous
Intraocular Pressure / drug effects
Laser-Doppler Flowmetry
Male
NG-Nitroarginine Methyl Ester / pharmacology
Optic Disk / blood supply*
Protein Kinase Inhibitors / administration & dosage*
Rabbits
Regional Blood Flow / drug effects
rho-Associated Kinases / antagonists & inhibitors*
Chemical
Reg. No./Substance:
0/Endothelin-1; 0/Protein Kinase Inhibitors; 103745-39-7/fasudil; 50903-99-6/NG-Nitroarginine Methyl Ester; 84477-87-2/1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; 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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