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Enhanced contractility of intraparenchymal arterioles after global cerebral ischaemia in rat - new insights into the development of delayed cerebral hypoperfusion

Spray, Stine; Johansson, S. E. LU ; Radziwon-Balicka, Aneta; Haanes, K A; Warfvinge, K. LU ; Povlsen, G. K.; Kelly, P. A T and Edvinsson, L. LU (2017) In Acta Physiologica2006-01-01+01:002013-01-01+01:00 220(4). p.417-431
Abstract

Aim: Delayed cerebral hypoperfusion is a secondary complication found in the days after transient global cerebral ischaemia that worsens the ischaemic damage inflicted by the initial transient episode of global cerebral ischaemia. A recent study demonstrated increased cerebral vasoconstriction in the large arteries on the brain surface (pial arteries) after global cerebral ischaemia. However, smaller arterioles inside the brain (parenchymal arterioles) are equally important in the regulation of cerebral blood flow and yet their pathophysiology after global cerebral ischaemia is largely unknown. Therefore, we investigated whether increased contractility occurs in the intraparenchymal arterioles. Methods: Global cerebral ischaemia was... (More)

Aim: Delayed cerebral hypoperfusion is a secondary complication found in the days after transient global cerebral ischaemia that worsens the ischaemic damage inflicted by the initial transient episode of global cerebral ischaemia. A recent study demonstrated increased cerebral vasoconstriction in the large arteries on the brain surface (pial arteries) after global cerebral ischaemia. However, smaller arterioles inside the brain (parenchymal arterioles) are equally important in the regulation of cerebral blood flow and yet their pathophysiology after global cerebral ischaemia is largely unknown. Therefore, we investigated whether increased contractility occurs in the intraparenchymal arterioles. Methods: Global cerebral ischaemia was induced in male Wistar rats by bilateral common carotid occlusion for 15 min combined with hypovolaemia. Regional cerebral blood flow was determined by quantitative autoradiography. Intraparenchymal arterioles were isolated and pressurized, and concentration-response curves to endothelin-1 with and without the endothelin B receptor-selective antagonist BQ788 was generated. Endothelin B receptor expression was investigated by quantitative flow cytometry and immunohistochemistry. Results: We observed increased endothelin-1-mediated contractility of parenchymal arterioles correlating with reduced cerebral blood flow of the cortex, hippocampus and caudate nucleus 48 h after global cerebral ischaemia. The increased endothelin-1-mediated contractility was abolished by BQ788, and the vascular smooth muscle cell-specific expression of endothelin B receptors was significantly increased after global cerebral ischaemia. Conclusion: Increased endothelin-1-mediated contractility and expression of endothelin B receptors in the intraparenchymal vasculature contributes to the development of delayed cerebral hypoperfusion after global cerebral ischaemia in combination with vascular changes of the pial vasculature.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Delayed cerebral hypoperfusion, Endothelin receptors, Endothelin-1, Global cerebral ischaemia, Intraparenchymal vasculature
in
Acta Physiologica2006-01-01+01:002013-01-01+01:00
volume
220
issue
4
pages
417 - 431
publisher
Wiley-Blackwell
external identifiers
  • scopus:85010764255
  • wos:000406110300005
ISSN
1748-1708
DOI
10.1111/apha.12834
language
English
LU publication?
yes
id
116a1dec-8275-4ff1-9051-f16e8ddcf4f5
date added to LUP
2017-02-27 09:14:54
date last changed
2018-07-08 04:21:50
@article{116a1dec-8275-4ff1-9051-f16e8ddcf4f5,
  abstract     = {<p>Aim: Delayed cerebral hypoperfusion is a secondary complication found in the days after transient global cerebral ischaemia that worsens the ischaemic damage inflicted by the initial transient episode of global cerebral ischaemia. A recent study demonstrated increased cerebral vasoconstriction in the large arteries on the brain surface (pial arteries) after global cerebral ischaemia. However, smaller arterioles inside the brain (parenchymal arterioles) are equally important in the regulation of cerebral blood flow and yet their pathophysiology after global cerebral ischaemia is largely unknown. Therefore, we investigated whether increased contractility occurs in the intraparenchymal arterioles. Methods: Global cerebral ischaemia was induced in male Wistar rats by bilateral common carotid occlusion for 15 min combined with hypovolaemia. Regional cerebral blood flow was determined by quantitative autoradiography. Intraparenchymal arterioles were isolated and pressurized, and concentration-response curves to endothelin-1 with and without the endothelin B receptor-selective antagonist BQ788 was generated. Endothelin B receptor expression was investigated by quantitative flow cytometry and immunohistochemistry. Results: We observed increased endothelin-1-mediated contractility of parenchymal arterioles correlating with reduced cerebral blood flow of the cortex, hippocampus and caudate nucleus 48 h after global cerebral ischaemia. The increased endothelin-1-mediated contractility was abolished by BQ788, and the vascular smooth muscle cell-specific expression of endothelin B receptors was significantly increased after global cerebral ischaemia. Conclusion: Increased endothelin-1-mediated contractility and expression of endothelin B receptors in the intraparenchymal vasculature contributes to the development of delayed cerebral hypoperfusion after global cerebral ischaemia in combination with vascular changes of the pial vasculature.</p>},
  author       = {Spray, Stine and Johansson, S. E. and Radziwon-Balicka, Aneta and Haanes, K A and Warfvinge, K. and Povlsen, G. K. and Kelly, P. A T and Edvinsson, L.},
  issn         = {1748-1708},
  keyword      = {Delayed cerebral hypoperfusion,Endothelin receptors,Endothelin-1,Global cerebral ischaemia,Intraparenchymal vasculature},
  language     = {eng},
  number       = {4},
  pages        = {417--431},
  publisher    = {Wiley-Blackwell},
  series       = {Acta Physiologica2006-01-01+01:002013-01-01+01:00},
  title        = {Enhanced contractility of intraparenchymal arterioles after global cerebral ischaemia in rat - new insights into the development of delayed cerebral hypoperfusion},
  url          = {http://dx.doi.org/10.1111/apha.12834},
  volume       = {220},
  year         = {2017},
}