ERK1/2 inhibition attenuates cerebral blood flow reduction and abolishes ET(B) and 5-HT(1B) receptor upregulation after subarachnoid hemorrhage in rat.

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Ansar, SaemaLund University,Lunds universitet,Medicin, Lund,Sektion II,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Medicine, Lund,Section II,Department of Clinical Sciences, Lund,Faculty of Medicine (author)

ERK1/2 inhibition attenuates cerebral blood flow reduction and abolishes ET(B) and 5-HT(1B) receptor upregulation after subarachnoid hemorrhage in rat.

Article/chapterEnglish2006

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2005-11-02
SAGE Publications,2006

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LIBRIS-ID:oai:lup.lub.lu.se:af3de89a-7929-4054-8765-ad2222b022b0
https://lup.lub.lu.se/record/148318URI
https://doi.org/10.1038/sj.jcbfm.9600236DOI

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Language:English
Summary in:English

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Upregulation of endothelin B (ETB) and 5-hydroxytryptamine 1B (5-HT1B) receptors via transcription has been found after experimental subarachnoid hemorrhage (SAH), and this is associated with enhanced phosphorylation of the mitogen-activated protein kinase ( MAPK) extracellular signal-regulated kinase ( ERK1/2). In the present study, we hypothesized that inhibition of ERK1/2 alters the ETB and 5-HT1B receptor upregulation and at the same time prevents the sustained cerebral blood flow (CBF) reduction associated with SAH. The ERK1/2 inhibitor SB386023-b was injected intracisternally in conjunction with and after the induced SAH in rats. At 2 days after the SAH, cerebral arteries were harvested for quantitative real-time polymerase chain reaction, immunohistochemistry and analysis of contractile responses to endothelin-1 (ET-1; ETA and ETB receptor agonist) and 5-carboxamidotryptamine (5-CT; 5-HT1 receptor agonist) in a sensitive myograph. To investigate if ERK1/2 inhibition had an influence on the local and global CBF after SAH, an autoradiographic technique was used. At 48 h after induced SAH, global and regional CBF were reduced by 50%. This reduction was prevented by treatment with SB386023-b. The ERK1/2 inhibition also decreased the maximum contraction elicited by application of ET-1 and 5-CT in cerebral arteries compared with SAH. In parallel, ERK1/2 inhibition downregulated ETB and 5-HT1B receptor messenger ribonucleic acid and protein levels compared with the SAH. Cerebral ischemia after SAH involves vasoconstriction and subsequent reduction in the CBF. The results suggest that ERK1/2 inhibition might be a potential treatment for the prevention of cerebral vasospasm and ischemia associated with SAH.

Subject headings and genre

MEDICIN OCH HÄLSOVETENSKAP Klinisk medicin Kardiologi hsv//swe
MEDICAL AND HEALTH SCIENCES Clinical Medicine Cardiac and Cardiovascular Systems hsv//eng
ETB receptor
cerebral blood flow (CBF)
cerebral ischemia
subarachnoid hemorrhage (SAH)
5-HT1B receptor
extracellular signal-regulated kinase (ERK1/2)

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Hansen-Schwartz, Jacob A (author)
Vikman, PetterLund University,Lunds universitet,Medicin, Lund,Sektion II,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Medicine, Lund,Section II,Department of Clinical Sciences, Lund,Faculty of Medicine(Swepub:lu)wbl-pwi (author)
Xu, Cang-BaoLund University,Lunds universitet,Medicin, Lund,Sektion II,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Medicine, Lund,Section II,Department of Clinical Sciences, Lund,Faculty of Medicine(Swepub:lu)med-cxu (author)
Edvinsson, LarsLund University,Lunds universitet,Medicin, Lund,Sektion II,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Medicine, Lund,Section II,Department of Clinical Sciences, Lund,Faculty of Medicine(Swepub:lu)med-led (author)
Medicin, LundSektion II (creator_code:org_t)

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In:Journal of Cerebral Blood Flow and Metabolism: SAGE Publications26:Nov 2, s. 846-8561559-70160271-678X

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By the author/editor: Ansar, Saema; Hansen-Schwartz, ...; Vikman, Petter; Xu, Cang-Bao; Edvinsson, Lars

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