This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Smeda, J. S. Articles by Harder, D. R. Search for Related Content PubMed PubMed Citation Articles by Smeda, J. S. Articles by Harder, D. R. Pubmed/NCBI databases Substance via MeSH Related Collections Animal models of human disease

(Stroke. 1999;30:656-661.)
© 1999 American Heart Association, Inc.

Original Contributions

Cerebrovascular Alterations in Protein Kinase C–Mediated Constriction in Stroke-Prone Rats

John S. Smeda, PhD Shelley King, MSc

From the Division of Basic Medical Sciences, Memorial University of Newfoundland, St John's, Newfoundland, Canada.

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 µmol/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 µmol/L], bisindolylmaleimide [5 µmol/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.

Editorial Comment

David R. Harder, PhD, Guest Editor

Cardiovascular Research Center, Medical College of Wisconsin, Milwaukee, Wisconsin

This article has been cited by other articles:

				J. S. Smeda Stroke Development in Stroke-Prone Spontaneously Hypertensive Rats Alters the Ability of Cerebrovascular Muscle to Utilize Internal Ca2+ to Elicit Constriction Stroke, June 1, 2003; 34(6): 1491 - 1496. [Abstract] [Full Text] [PDF]

				J. S. Smeda, S. King, and G. Osol Electromechanical Alterations in the Cerebrovasculature of Stroke-Prone Rats • Editorial Comment Stroke, March 1, 2000; 31(3): 751 - 759. [Abstract] [Full Text] [PDF]