Document Detail


Thin and thick filament regulation of contractility in experimental cerebral vasospasm.
MedLine Citation:
PMID:  10690734     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVE: Cerebral vasospasm is a potentially fatal consequence of aneurysmal subarachnoid hemorrhage and influences the prognosis of the patient. The purpose of this study was to evaluate the status of thin (actin) and thick (myosin) filament regulation of smooth muscle contraction in the double-subarachnoid hemorrhage canine model of cerebral vasospasm and to determine the effects of a kinase inhibitor reported to be effective in vasospasm, HA1077, on thin and thick filament regulation. METHODS: Cerebral vasospasm was assessed by vertebral angiography. Myosin regulatory light chain phosphorylation was measured using glycerol-urea gels, whereas protein levels of the thin filament-associated protein calponin were measured by Western blot. RESULTS: The basilar arteries of dogs in which subarachnoid hemorrhage was induced narrowed to 36% +/- 2.0% of their size on the first day (n = 12). The phosphorylation of the regulatory light chain tended to increase, but the change did not reach statistical significance (35% +/- 5.9% [n = 12] versus 25% +/- 4.8% [n = 10] in control arteries). In contrast to this increase, significant degradation of calponin was observed in the samples from vasospastic dogs (85.4% +/- 5.45% [n = 5] versus 15.2% +/- 6.21% [n = 5]; P < 0.01). Prophylactic treatment with intravenous injections of HA1077 at 0.67 mg/kg b.i.d. significantly inhibited vasospasm (diameters, 65% +/- 10.2% of Day 1 diameters [n = 5]; P < 0.05), and calponin degradation (57.8% +/- 13.9% [n = 4]) was substantially reduced. CONCLUSION: These data suggest that degradation of the thin filament-associated protein calponin plays a role in cerebral vasospasm and that the antivasospastic action of HA1077 is, at least in part, due to prevention of calponin degradation.
Authors:
I Kim; B D Leinweber; M Morgalla; W E Butler; M Seto; Y Sasaki; J W Peterson; K G Morgan
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Neurosurgery     Volume:  46     ISSN:  0148-396X     ISO Abbreviation:  Neurosurgery     Publication Date:  2000 Feb 
Date Detail:
Created Date:  2000-03-23     Completed Date:  2000-03-23     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  7802914     Medline TA:  Neurosurgery     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  440-6; discussion 446-7     Citation Subset:  IM    
Affiliation:
Signal Transduction Group, Boston Biomedical Research Institute Massachusetts 02114-2500, USA.
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MeSH Terms
Descriptor/Qualifier:
1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / analogs & derivatives*,  pharmacology
Actins / physiology*
Animals
Basilar Artery / drug effects,  physiopathology
Calcium-Binding Proteins / physiology
Dogs
Microfilament Proteins
Muscle, Smooth, Vascular / drug effects,  physiopathology*
Myosin Light Chains / physiology
Myosins / physiology*
Subarachnoid Hemorrhage / physiopathology
Vasoconstriction / drug effects,  physiology*
Vasodilator Agents / pharmacology*
Vasospasm, Intracranial / physiopathology*
Grant Support
ID/Acronym/Agency:
HL31704/HL/NHLBI NIH HHS; HL42293/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Actins; 0/Calcium-Binding Proteins; 0/Microfilament Proteins; 0/Myosin Light Chains; 0/Vasodilator Agents; 0/calponin; 103745-39-7/fasudil; 84477-87-2/1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; EC 3.6.4.1/Myosins

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