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

Gro Klitgaard Povlsen, Roya Waldsee, Hilda Ahnstedt, Kim Anker Kristiansen, Flemming Fryd Johansen, Lars Edvinsson

Research output: Contribution to journalArticlepeer-review

17 Citations (SciVal)

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 < 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.
Original languageEnglish
Pages (from-to)507-520
JournalExperimental Brain Research
Volume219
Issue number4
DOIs
Publication statusPublished - 2012

Subject classification (UKÄ)

  • Neurosciences

Keywords

  • Experimental stroke
  • Vascular smooth muscle
  • Endothelin B receptor
  • 5-hydroxytryptamine 1B receptor
  • Intracellular calcium
  • Calcium channels

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