Document Detail


Na+/H+ exchange inhibitor SM-20220 improves endothelial dysfunction induced by ischemia-reperfusion.
MedLine Citation:
PMID:  11325019     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Endothelial cells play an important role in the physiologic homeostasis of the cerebral circulation. Previously, we showed that the Na+/H+ exchanger (NHE) inhibitor SM-20220 (N-(aminoimino-methyl)-1-methyl-1H-indole-2-carboxamide methanesulfonate) improved ischemic brain injury. In this study, we investigated the effect of SM-20220 on cerebrovascular dysfunction after ischemia-reperfusion, focusing on the kinds of dysfunction that involved endothelial function. In cultured bovine brain microvascular endothelial cells (BBMCs), the IC50 value for the NHE activity of SM-20220 was 4 x 10(-8) M. SM-20220 also reduced the cell injury induced by hypoxia/aglycemia-reoxygenation in BBMCs, with statistical significance at 10(-7) M (P<0.05). Next, the effect of SM-20220 on disruption of the blood-brain barrier and cerebral blood flow were evaluated using transient middle cerebral artery (MCA) occlusion models. Intravenous infusion of SM-20220 (0.4 mg/kg per hour for 1 h) attenuated the extravasation of Evans blue, a blood-brain barrier disruption indicator, into cerebral tissue on the day after transient ischemia (P<0.05). The occlusion of the MCA decreased the cerebral blood flow in the MCA territory by about 20%, and only about 45% of the preischemic value was recovered at 1-h reperfusion. A bolus injection of SM-20220 (1 mg/kg, i.v.) improved the postischemic hypoperfusion by about 75%, without causing changes in the systemic blood pressure. These results indicate that the protective effect of NHE inhibitor on ischemic brain injury may be at least partially mediated by the prevention of endothelial dysfunction.
Authors:
N Horikawa; Y Kuribayashi; N Itoh; M Nishioka; K Matsui; N Kawamura; N Ohashi
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Japanese journal of pharmacology     Volume:  85     ISSN:  0021-5198     ISO Abbreviation:  Jpn. J. Pharmacol.     Publication Date:  2001 Mar 
Date Detail:
Created Date:  2001-04-27     Completed Date:  2001-08-23     Revised Date:  2005-11-17    
Medline Journal Info:
Nlm Unique ID:  2983305R     Medline TA:  Jpn J Pharmacol     Country:  Japan    
Other Details:
Languages:  eng     Pagination:  271-7     Citation Subset:  IM    
Affiliation:
Sumitomo Pharmaceuticals Research Division, Osaka, Japan.
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MeSH Terms
Descriptor/Qualifier:
Amides / pharmacology*
Animals
Arterial Occlusive Diseases / complications
Blood Pressure
Blood-Brain Barrier
Brain / blood supply
Brain Ischemia / etiology,  physiopathology,  prevention & control*
Cattle
Cell Hypoxia
Cells, Cultured
Cerebral Arterial Diseases / complications
Coloring Agents
Cytoprotection
Endothelium, Vascular / drug effects*,  metabolism
Evans Blue
Indoles / pharmacology*
Microcirculation
Middle Cerebral Artery
Rats
Rats, Wistar
Regional Blood Flow
Reperfusion Injury / metabolism,  physiopathology,  prevention & control*
Sodium-Hydrogen Antiporter / antagonists & inhibitors*
Chemical
Reg. No./Substance:
0/Amides; 0/Coloring Agents; 0/Indoles; 0/SM 20220; 0/Sodium-Hydrogen Antiporter; 314-13-6/Evans Blue

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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