Document Detail

Cerebrovascular alterations in protein kinase C-mediated constriction in stroke-prone rats.
MedLine Citation:
PMID:  10066867     Owner:  NLM     Status:  MEDLINE    
BACKGROUND AND PURPOSE: Cerebrovascular pressure-dependent constriction may involve the smooth muscle production of diacylglycerol, which could facilitate constriction by activating protein kinase C (PKC). A dysfunctional PKC system could promote the loss of pressure-dependent constriction. We attempted to determine whether the alterations in pressure-dependent constriction in the middle cerebral arteries (MCAs) observed in relation to stroke development in Wistar-Kyoto stroke-prone spontaneously hypertensive rats (SHRsp) were associated with defects in the ability of the arteries to constrict in response to PKC activation. METHODS: MCAs were sampled from SHRsp before and after stroke development and in stroke-resistant Wistar-Kyoto spontaneously hypertensive rats. A pressure myograph was used to test the ability of the arteries to constrict in response to a 100 mm Hg pressure step and subsequently to contract in response to phorbol 12,13-dibutyrate in the presence of nifedipine (3 micromol/L). RESULTS: Pressure-dependent constriction and constriction in response to phorbol dibutyrate in the MCAs were inhibited by PKC inhibitors (staurosporine [40 nmol/L], chelerythrine [12 micromol/L], bisindolylmaleimide [5 micromol/L]), declined with age before stroke development in SHRsp, and were absent after stroke. There was a significant relationship between pressure- and phorbol dibutyrate-induced constriction (r=0.815, P<0. 05). CONCLUSIONS: Phorbol esters interact with the same activation site as diacylglycerol to stimulate PKC. An inability to constrict in response to phorbol dibutyrate may reflect unresponsiveness to diacylglycerol and may contribute to the loss of pressure-dependent constriction associated with stroke in the MCAs of SHRsp. The loss of this autoregulatory function before stroke could increase the risk of cerebral hemorrhage.
J S Smeda; S King; D R Harder
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Stroke; a journal of cerebral circulation     Volume:  30     ISSN:  0039-2499     ISO Abbreviation:  Stroke     Publication Date:  1999 Mar 
Date Detail:
Created Date:  1999-04-13     Completed Date:  1999-04-13     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  0235266     Medline TA:  Stroke     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  656-61     Citation Subset:  IM    
Division of Basic Medical Sciences, Memorial University of Newfoundland, St John's, Newfoundland, Canada.
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MeSH Terms
Cerebral Arteries / physiopathology*
Cerebrovascular Disorders / etiology*
Protein Kinase C / physiology*
Rats, Inbred SHR
Rats, Inbred WKY
Vasoconstriction / physiology*
Reg. No./Substance:
EC Kinase C

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

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