Protein kinase C inhibition prevents upregulation of vascular ET(B) and 5-HT(1B) receptors and reverses cerebral blood flow reduction after subarachnoid haemorrhage in rats.
(2007) In Journal of Cerebral Blood Flow and Metabolism 27(1). p.21-32- Abstract
- The pathogenesis of cerebral ischaemia after subarachnoid haemorrhage (SAH) still remains elusive. The purpose of the present study was to examine whether specific protein kinas C (PKC) inhibition in rats could alter the transcriptional SAH induced Endothelin (ET) type B and 5-hydroxytryptamine type 1B (5-HT1B) receptor upregulation and prevent the associated cerebral blood flow (CBF) reduction. The PKC inhibitor RO-31-7549 or vehicle was injected intracisternally after the induced SAH in rats (n = 3 to 10 in each groups for each method). The involvement of the PKC isoforms was investigated with Western blot; only PKC delta and PKC alpha subtypes were increased after SAH RO-31-7549 treatment abolished this. At 2 days after the SAH basilar... (More)
- The pathogenesis of cerebral ischaemia after subarachnoid haemorrhage (SAH) still remains elusive. The purpose of the present study was to examine whether specific protein kinas C (PKC) inhibition in rats could alter the transcriptional SAH induced Endothelin (ET) type B and 5-hydroxytryptamine type 1B (5-HT1B) receptor upregulation and prevent the associated cerebral blood flow (CBF) reduction. The PKC inhibitor RO-31-7549 or vehicle was injected intracisternally after the induced SAH in rats (n = 3 to 10 in each groups for each method). The involvement of the PKC isoforms was investigated with Western blot; only PKC delta and PKC alpha subtypes were increased after SAH RO-31-7549 treatment abolished this. At 2 days after the SAH basilar and middle cerebral arteries were harvested and the contractile response to endothelin-1 (ET-1; ETA and ETB receptor agonist) and 5-carboxamidotryptamine (5-CT; 5-HT1B receptor agonist) were investigated with a myograph. The contractile responses to ET-1 and 5-CT were increased (P < 0.05) after SAH compared with sham operated rats. In parallel, the ETB and 5-HT1B receptor mRNA and protein expression were significantly elevated after SAH, as analysed by quantitative real-time polymerase chain reaction and immunohistochemistry, respectively. Administration of RO-31-7549 prevented the upregulated contraction elicited by application of ET-1 and 5-CT in cerebral arteries and kept the ETB and 5-HT1B receptor mRNA and protein levels at pre-SAH levels. Regional and global CBF evaluated by an autoradiographic technique were reduced by 60% 64% after SAH (P < 0.05) and prevented by treatment with RO-31-7549. Our study suggests that PKC plays an important role in the pathogenesis of cerebral ischaemia after SAH. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/158549
- author
- Ansar, Saema LU ; Hansen-Schwartz, Jacob A ; Vikman, Petter LU ; Xu, Cang-Bao LU and Edvinsson, Lars LU
- organization
- publishing date
- 2007
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- subarachnoid haemorrhage, cerebral ischaemia, ETB receptor, cerebral blood flow, 5-HT1B receptor, protein kinase C
- in
- Journal of Cerebral Blood Flow and Metabolism
- volume
- 27
- issue
- 1
- pages
- 21 - 32
- publisher
- Nature Publishing Group
- external identifiers
-
- wos:000242934200004
- scopus:33845775387
- ISSN
- 1559-7016
- DOI
- 10.1038/sj.jcbfm.9600313
- language
- English
- LU publication?
- yes
- id
- 390aae28-b2b2-4ffe-b093-ee258a5be922 (old id 158549)
- alternative location
- http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=16736053&dopt=Abstract
- date added to LUP
- 2016-04-01 16:56:36
- date last changed
- 2024-10-12 06:38:37
@article{390aae28-b2b2-4ffe-b093-ee258a5be922,
abstract = {{The pathogenesis of cerebral ischaemia after subarachnoid haemorrhage (SAH) still remains elusive. The purpose of the present study was to examine whether specific protein kinas C (PKC) inhibition in rats could alter the transcriptional SAH induced Endothelin (ET) type B and 5-hydroxytryptamine type 1B (5-HT1B) receptor upregulation and prevent the associated cerebral blood flow (CBF) reduction. The PKC inhibitor RO-31-7549 or vehicle was injected intracisternally after the induced SAH in rats (n = 3 to 10 in each groups for each method). The involvement of the PKC isoforms was investigated with Western blot; only PKC delta and PKC alpha subtypes were increased after SAH RO-31-7549 treatment abolished this. At 2 days after the SAH basilar and middle cerebral arteries were harvested and the contractile response to endothelin-1 (ET-1; ETA and ETB receptor agonist) and 5-carboxamidotryptamine (5-CT; 5-HT1B receptor agonist) were investigated with a myograph. The contractile responses to ET-1 and 5-CT were increased (P < 0.05) after SAH compared with sham operated rats. In parallel, the ETB and 5-HT1B receptor mRNA and protein expression were significantly elevated after SAH, as analysed by quantitative real-time polymerase chain reaction and immunohistochemistry, respectively. Administration of RO-31-7549 prevented the upregulated contraction elicited by application of ET-1 and 5-CT in cerebral arteries and kept the ETB and 5-HT1B receptor mRNA and protein levels at pre-SAH levels. Regional and global CBF evaluated by an autoradiographic technique were reduced by 60% 64% after SAH (P < 0.05) and prevented by treatment with RO-31-7549. Our study suggests that PKC plays an important role in the pathogenesis of cerebral ischaemia after SAH.}},
author = {{Ansar, Saema and Hansen-Schwartz, Jacob A and Vikman, Petter and Xu, Cang-Bao and Edvinsson, Lars}},
issn = {{1559-7016}},
keywords = {{subarachnoid haemorrhage; cerebral ischaemia; ETB receptor; cerebral blood flow; 5-HT1B receptor; protein kinase C}},
language = {{eng}},
number = {{1}},
pages = {{21--32}},
publisher = {{Nature Publishing Group}},
series = {{Journal of Cerebral Blood Flow and Metabolism}},
title = {{Protein kinase C inhibition prevents upregulation of vascular ET(B) and 5-HT(1B) receptors and reverses cerebral blood flow reduction after subarachnoid haemorrhage in rats.}},
url = {{http://dx.doi.org/10.1038/sj.jcbfm.9600313}},
doi = {{10.1038/sj.jcbfm.9600313}},
volume = {{27}},
year = {{2007}},
}