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Cerebrovascular ETB, 5-HT1B and AT1 Receptor Upregulation Correlates with Reduction in Regional CBF after Subarachnoid Hemorrhage.

Ansar, Saema LU ; Vikman, Petter LU ; Nielsen, Marianne and Edvinsson, Lars LU (2007) In American Journal of Physiology: Heart and Circulatory Physiology 293(6). p.3750-3758
Abstract
We hypothesize that cerebral ischemia leads to enhanced expression of endothelin (ET), 5-hydroxytryptamine (5-HT), and angiotensin II (ANG II) receptors in the vascular smooth muscle cells. Our aim is to correlate the upregulation of cerebrovascular receptors and the underlying molecular mechanisms with the reduction in regional and global cerebral blood flow (CBF) after subarachnoid hemorrhage (SAH). SAH was induced by injecting 250 µl blood into the prechiasmatic cistern in rats. The cerebral arteries were removed 0, 1, 3, 6, 12, 24, and 48 h after the SAH for functional and molecular studies. The contractile responses to ET-1, 5-carboxamidotryptamine (5-CT), and ANG II were investigated with myograph. The receptor mRNA and protein... (More)
We hypothesize that cerebral ischemia leads to enhanced expression of endothelin (ET), 5-hydroxytryptamine (5-HT), and angiotensin II (ANG II) receptors in the vascular smooth muscle cells. Our aim is to correlate the upregulation of cerebrovascular receptors and the underlying molecular mechanisms with the reduction in regional and global cerebral blood flow (CBF) after subarachnoid hemorrhage (SAH). SAH was induced by injecting 250 µl blood into the prechiasmatic cistern in rats. The cerebral arteries were removed 0, 1, 3, 6, 12, 24, and 48 h after the SAH for functional and molecular studies. The contractile responses to ET-1, 5-carboxamidotryptamine (5-CT), and ANG II were investigated with myograph. The receptor mRNA and protein levels were analyzed by quantitative real-time PCR and immunohistochemistry, respectively. In addition, regional and global CBFs were measured by an autoradiographic method. As a result, SAH resulted in enhanced contractions to ET-1 and 5-CT. ANG II [via ANG II type 1 (AT1) receptors] induced increased contractile responses [in the presence of the ANG II type 2 (AT2) receptor antagonist PD-123319]. In parallel the ETB, 5-HT1B, and AT1 receptor, mRNA and protein levels were elevated by time. The regional and global CBF showed a successive reduction with time after SAH. In conclusion, the results demonstrate for the first time that SAH induces the upregulation of ETB, 5-HT1B, and AT1 receptors in a time-dependent manner both at functional, mRNA, and protein levels. These changes occur in parallel with a successive decrease in CBF. Thus there is a temporal correlation between the changes in receptor expression and CBF reduction, suggesting a linkage. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
American Journal of Physiology: Heart and Circulatory Physiology
volume
293
issue
6
pages
3750 - 3758
publisher
American Physiological Society
external identifiers
  • wos:000251400300063
  • scopus:36849086026
ISSN
1522-1539
DOI
10.1152/ajpheart.00857.2007
language
English
LU publication?
yes
id
fa4ff7b8-3847-4347-906f-4fd9b589b3c9 (old id 607719)
alternative location
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=17873013&dopt=Abstract
date added to LUP
2008-01-22 13:31:17
date last changed
2017-11-19 03:37:19
@article{fa4ff7b8-3847-4347-906f-4fd9b589b3c9,
  abstract     = {We hypothesize that cerebral ischemia leads to enhanced expression of endothelin (ET), 5-hydroxytryptamine (5-HT), and angiotensin II (ANG II) receptors in the vascular smooth muscle cells. Our aim is to correlate the upregulation of cerebrovascular receptors and the underlying molecular mechanisms with the reduction in regional and global cerebral blood flow (CBF) after subarachnoid hemorrhage (SAH). SAH was induced by injecting 250 µl blood into the prechiasmatic cistern in rats. The cerebral arteries were removed 0, 1, 3, 6, 12, 24, and 48 h after the SAH for functional and molecular studies. The contractile responses to ET-1, 5-carboxamidotryptamine (5-CT), and ANG II were investigated with myograph. The receptor mRNA and protein levels were analyzed by quantitative real-time PCR and immunohistochemistry, respectively. In addition, regional and global CBFs were measured by an autoradiographic method. As a result, SAH resulted in enhanced contractions to ET-1 and 5-CT. ANG II [via ANG II type 1 (AT1) receptors] induced increased contractile responses [in the presence of the ANG II type 2 (AT2) receptor antagonist PD-123319]. In parallel the ETB, 5-HT1B, and AT1 receptor, mRNA and protein levels were elevated by time. The regional and global CBF showed a successive reduction with time after SAH. In conclusion, the results demonstrate for the first time that SAH induces the upregulation of ETB, 5-HT1B, and AT1 receptors in a time-dependent manner both at functional, mRNA, and protein levels. These changes occur in parallel with a successive decrease in CBF. Thus there is a temporal correlation between the changes in receptor expression and CBF reduction, suggesting a linkage.},
  author       = {Ansar, Saema and Vikman, Petter and Nielsen, Marianne and Edvinsson, Lars},
  issn         = {1522-1539},
  language     = {eng},
  number       = {6},
  pages        = {3750--3758},
  publisher    = {American Physiological Society},
  series       = {American Journal of Physiology: Heart and Circulatory Physiology},
  title        = {Cerebrovascular ETB, 5-HT1B and AT1 Receptor Upregulation Correlates with Reduction in Regional CBF after Subarachnoid Hemorrhage.},
  url          = {http://dx.doi.org/10.1152/ajpheart.00857.2007},
  volume       = {293},
  year         = {2007},
}