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.

Summary, in English

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.

• Författare: Saema Ansar; Jacob A Hansen-Schwartz; Petter Vikman; Cang-Bao Xu; Lars Edvinsson
• Avdelning/ar: Medicin/akutsjukvård, Lund
• Publiceringsår: 2007
• Språk: Engelska
• Sidor: 21-32
• Publikation/Tidskrift/Serie: Journal of Cerebral Blood Flow and Metabolism
• Volym: 27
• Issue: 1
• Länkar: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=16736053&dopt=Abstract; http://dx.doi.org/10.1038/sj.jcbfm.9600313
• Dokumenttyp: Artikel i tidskrift
• Förlag: Nature Publishing Group
• Ämne: Cardiac and Cardiovascular Systems
• Nyckelord: subarachnoid haemorrhage; cerebral ischaemia; ETB receptor; cerebral blood flow; 5-HT1B receptor; protein kinase C
• Status: Published
• ISBN/ISSN/Övrigt: ISSN: 1559-7016