Document Detail


Oxyhemoglobin-induced expression of R-type Ca2+ channels in cerebral arteries.
MedLine Citation:
PMID:  18436877     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND AND PURPOSE: Cerebral vasospasm after subarachnoid hemorrhage (SAH) is a major contributor to mortality and morbidity after aneurysm rupture. Recently, R-type voltage-dependent Ca(2+) channel (VDCC) expression has been associated with increased cerebral artery constriction in a rabbit model of SAH. The goal of the present study was to examine whether the blood component oxyhemoglobin (oxyHb) can mimic the ability of SAH to cause R-type VDCC expression in the cerebral vasculature.
METHODS: Rabbit cerebral arteries were organ cultured in serum-free media for up to 5 days in the presence or absence of purified oxyHb (10 micromol/L). Diameter changes in response to diltiazem, (L-type VDCC antagonist) and SNX-482 (R-type VDCC antagonist) were recorded at day 1, 3, or 5 in arteries constricted by elevated extracellular potassium. RT-PCR was performed on RNA extracted from arteries cultured for 5 days (+/-oxyHb) to assess VDCC expression.
RESULTS: After 5 days, oxyHb-treated arteries were less sensitive and partially resistant to diltiazem compared to similar arteries organ cultured in the absence of oxyHb. Further, SNX-482 dilated arteries organ cultured for 5 days in the presence, but not in the absence, of oxyHb. RT-PCR revealed that oxyHb treated arteries expressed R-type VDCCs (Ca(V) 2.3) in addition to L-type VDCCs (Ca(V) 1.2), whereas untreated arteries expressed only Ca(V) 1.2.
CONCLUSIONS: These results demonstrate that oxyhemoglobin exposure for 5 days induces the expression of Ca(V) 2.3 in cerebral arteries. We propose that oxyhemoglobin contributes to enhanced cerebral artery constriction after SAH via the emergence of R-type VDCCs.
Authors:
Timothy E Link; Kentaro Murakami; Micah Beem-Miller; Bruce I Tranmer; George C Wellman
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2008-04-24
Journal Detail:
Title:  Stroke; a journal of cerebral circulation     Volume:  39     ISSN:  1524-4628     ISO Abbreviation:  Stroke     Publication Date:  2008 Jul 
Date Detail:
Created Date:  2008-06-24     Completed Date:  2008-07-23     Revised Date:  2013-05-21    
Medline Journal Info:
Nlm Unique ID:  0235266     Medline TA:  Stroke     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2122-8     Citation Subset:  IM    
Affiliation:
Department of Pharmacology, University of Vermont College of Medicine, 86 Beaumont Ave, Burlington, VT 05405, USA.
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MeSH Terms
Descriptor/Qualifier:
Aneurysm / metabolism
Animals
Calcium Channel Blockers / pharmacology
Calcium Channels / metabolism*
Cerebral Arteries / metabolism*
Culture Media, Serum-Free / pharmacology
Diltiazem / pharmacology
Endothelium, Vascular / metabolism
Gene Expression Regulation*
Male
Muscle, Smooth / metabolism
Oxyhemoglobins / biosynthesis*
Rabbits
Subarachnoid Hemorrhage / metabolism
Grant Support
ID/Acronym/Agency:
P20 RR016435/RR/NCRR NIH HHS; P20 RR016435-060005/RR/NCRR NIH HHS; P20 RR16435/RR/NCRR NIH HHS; R01 HL078983/HL/NHLBI NIH HHS; R01 HL078983/HL/NHLBI NIH HHS; R01 HL078983-02/HL/NHLBI NIH HHS; R01 HL078983-03/HL/NHLBI NIH HHS; R01 HL078983-04/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Calcium Channel Blockers; 0/Calcium Channels; 0/Culture Media, Serum-Free; 0/Oxyhemoglobins; 42399-41-7/Diltiazem
Comments/Corrections

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