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In vivo experimental stroke and in vitro organ culture induce similar changes in vasoconstrictor receptors and intracellular calcium handling in rat cerebral arteries

Povlsen, Gro Klitgaard; Waldsee, Roya LU ; Ahnstedt, Hilda LU ; Kristiansen, Kim Anker; Johansen, Flemming Fryd and Edvinsson, Lars (2012) In Experimental Brain Research 219(4). p.507-520
Abstract
Cerebral arteries subjected to different types of experimental stroke upregulate their expression of certain G-protein-coupled vasoconstrictor receptors, a phenomenon that worsens the ischemic brain damage. Upregulation of contractile endothelin B (ETB) and 5-hydroxytryptamine 1B (5-HT1B) receptors has been demonstrated after subarachnoid hemorrhage and global ischemic stroke, but the situation is less clear after focal ischemic stroke. Changes in smooth muscle calcium handling have been implicated in different vascular diseases but have not hitherto been investigated in cerebral arteries after stroke. Here, we evaluate changes of ETB and 5-HT1B receptors, intracellular calcium levels, and calcium channel expression in rat middle cerebral... (More)
Cerebral arteries subjected to different types of experimental stroke upregulate their expression of certain G-protein-coupled vasoconstrictor receptors, a phenomenon that worsens the ischemic brain damage. Upregulation of contractile endothelin B (ETB) and 5-hydroxytryptamine 1B (5-HT1B) receptors has been demonstrated after subarachnoid hemorrhage and global ischemic stroke, but the situation is less clear after focal ischemic stroke. Changes in smooth muscle calcium handling have been implicated in different vascular diseases but have not hitherto been investigated in cerebral arteries after stroke. Here, we evaluate changes of ETB and 5-HT1B receptors, intracellular calcium levels, and calcium channel expression in rat middle cerebral artery (MCA) after focal cerebral ischemia and in vitro organ culture, a proposed model of vasoconstrictor receptor changes after stroke. Rats were subjected to 2 h MCA occlusion followed by reperfusion for 1 or 24 h. Alternatively, MCAs from na < ve rats were cultured for 1 or 24 h. ETB and 5-HT1B receptor-mediated contractions were evaluated by wire myography. Receptor and channel expressions were measured by real-time PCR and immunohistochemistry. Intracellular calcium was measured by FURA-2. Expression and contractile functions of ETB and 5-HT1B receptors were strongly upregulated and slightly downregulated, respectively, 24 h after experimental stroke or organ culture. ETB receptor-mediated contraction was mediated by calcium from intracellular and extracellular sources, whereas 5-HT1B receptor-mediated contraction was solely dependent on extracellular calcium. Organ culture and stroke increased basal intracellular calcium levels in MCA smooth muscle cells and decreased the expression of inositol triphosphate receptor and transient receptor potential canonical calcium channels, but not voltage-operated calcium channels. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Experimental stroke, Vascular smooth muscle, Endothelin B receptor, 5-hydroxytryptamine 1B receptor, Intracellular calcium, Calcium channels
in
Experimental Brain Research
volume
219
issue
4
pages
507 - 520
publisher
Springer
external identifiers
  • wos:000304855800010
  • scopus:84875582669
ISSN
0014-4819
DOI
10.1007/s00221-012-3108-6
language
English
LU publication?
yes
id
91272ee5-336a-41bf-8826-fbd734950bc8 (old id 2896869)
date added to LUP
2012-08-01 09:43:43
date last changed
2017-05-28 03:22:33
@article{91272ee5-336a-41bf-8826-fbd734950bc8,
  abstract     = {Cerebral arteries subjected to different types of experimental stroke upregulate their expression of certain G-protein-coupled vasoconstrictor receptors, a phenomenon that worsens the ischemic brain damage. Upregulation of contractile endothelin B (ETB) and 5-hydroxytryptamine 1B (5-HT1B) receptors has been demonstrated after subarachnoid hemorrhage and global ischemic stroke, but the situation is less clear after focal ischemic stroke. Changes in smooth muscle calcium handling have been implicated in different vascular diseases but have not hitherto been investigated in cerebral arteries after stroke. Here, we evaluate changes of ETB and 5-HT1B receptors, intracellular calcium levels, and calcium channel expression in rat middle cerebral artery (MCA) after focal cerebral ischemia and in vitro organ culture, a proposed model of vasoconstrictor receptor changes after stroke. Rats were subjected to 2 h MCA occlusion followed by reperfusion for 1 or 24 h. Alternatively, MCAs from na &lt; ve rats were cultured for 1 or 24 h. ETB and 5-HT1B receptor-mediated contractions were evaluated by wire myography. Receptor and channel expressions were measured by real-time PCR and immunohistochemistry. Intracellular calcium was measured by FURA-2. Expression and contractile functions of ETB and 5-HT1B receptors were strongly upregulated and slightly downregulated, respectively, 24 h after experimental stroke or organ culture. ETB receptor-mediated contraction was mediated by calcium from intracellular and extracellular sources, whereas 5-HT1B receptor-mediated contraction was solely dependent on extracellular calcium. Organ culture and stroke increased basal intracellular calcium levels in MCA smooth muscle cells and decreased the expression of inositol triphosphate receptor and transient receptor potential canonical calcium channels, but not voltage-operated calcium channels.},
  author       = {Povlsen, Gro Klitgaard and Waldsee, Roya and Ahnstedt, Hilda and Kristiansen, Kim Anker and Johansen, Flemming Fryd and Edvinsson, Lars},
  issn         = {0014-4819},
  keyword      = {Experimental stroke,Vascular smooth muscle,Endothelin B receptor,5-hydroxytryptamine 1B receptor,Intracellular calcium,Calcium channels},
  language     = {eng},
  number       = {4},
  pages        = {507--520},
  publisher    = {Springer},
  series       = {Experimental Brain Research},
  title        = {In vivo experimental stroke and in vitro organ culture induce similar changes in vasoconstrictor receptors and intracellular calcium handling in rat cerebral arteries},
  url          = {http://dx.doi.org/10.1007/s00221-012-3108-6},
  volume       = {219},
  year         = {2012},
}