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Cooperative effect of angiotensin AT, and endothelin ETA receptor antagonism limits the brain damage after ischemic stroke in rat

Stenman, Emelie LU ; Waldsee, Roya LU ; Henriksson, Marie LU ; Maddahi, Aida LU and Edvinsson, Lars LU (2007) In European Journal of Pharmacology 570(1-3). p.142-148
Abstract
Cerebral ischemia results in enhanced expression of smooth muscle cell endothelin and angiotensin receptors in cerebral arteries. We hypothesise that this phenomenon may be detrimental and that acute treatment with a combined non-hypotensive dose of the angiotensin AT, receptor inhibitor candesartan and the endothelin ETA receptor antagonist ZD 1611 reduces the infarct in experimental ischemic stroke. Transient middle cerebral artery occlusion was induced in male Wistar rats by the intraluminal filament technique for 2 h followed by recirculation. The animals received systemic candesartan (0.05 mg/kg/day), ZD1611 (0.15 mg/kg/day), both combined or vehicle with start immediately after the occlusion. After 48 h the rats were sacrificed, the... (More)
Cerebral ischemia results in enhanced expression of smooth muscle cell endothelin and angiotensin receptors in cerebral arteries. We hypothesise that this phenomenon may be detrimental and that acute treatment with a combined non-hypotensive dose of the angiotensin AT, receptor inhibitor candesartan and the endothelin ETA receptor antagonist ZD 1611 reduces the infarct in experimental ischemic stroke. Transient middle cerebral artery occlusion was induced in male Wistar rats by the intraluminal filament technique for 2 h followed by recirculation. The animals received systemic candesartan (0.05 mg/kg/day), ZD1611 (0.15 mg/kg/day), both combined or vehicle with start immediately after the occlusion. After 48 h the rats were sacrificed, the brains sliced and stained with 1% 2, 3, 5-triphenyltetrazolium chloride (TTC) and the volume of ischemic damage determined. The middle cerebral arteries were harvested for immunocytochemical studies of angiotensin AT, and endothelin ETA receptor expression. Candesartan or ZD1611 did alone not significantly decrease the brain damage or improve neurological scores as compared to vehicle controls. The combined inhibition of angiotensin AT, and endothelin ETA receptors however decreased the brain damage and improved the neurological scores (both P < 0.05). The treatment did not change resting mean arterial blood pressure. In addition, there was an upregulation of angiotensin AT, receptors in the ischemic middle cerebral artery smooth muscle cells, which was normalised by the combined treatment. In conclusion, the present study shows that combined inhibition of angiotensin AT, and endothelin ETA receptors reduces the brain damage and improves the neurological outcome after ischemic stroke in rat. (c) 2007 Elsevier B.V. All rights reserved. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
angiotensin AT(1) receptor, candesartan, ZD1611, cerebral ischemia, (Rat), endothelin ETA receptor
in
European Journal of Pharmacology
volume
570
issue
1-3
pages
142 - 148
publisher
Elsevier
external identifiers
  • wos:000249295100019
  • scopus:34547903660
ISSN
1879-0712
DOI
10.1016/j.ejphar.2007.05.049
language
English
LU publication?
yes
id
4922850b-be9e-4780-88c6-4d124cf96559 (old id 686650)
date added to LUP
2007-12-19 10:07:22
date last changed
2017-01-01 05:09:41
@article{4922850b-be9e-4780-88c6-4d124cf96559,
  abstract     = {Cerebral ischemia results in enhanced expression of smooth muscle cell endothelin and angiotensin receptors in cerebral arteries. We hypothesise that this phenomenon may be detrimental and that acute treatment with a combined non-hypotensive dose of the angiotensin AT, receptor inhibitor candesartan and the endothelin ETA receptor antagonist ZD 1611 reduces the infarct in experimental ischemic stroke. Transient middle cerebral artery occlusion was induced in male Wistar rats by the intraluminal filament technique for 2 h followed by recirculation. The animals received systemic candesartan (0.05 mg/kg/day), ZD1611 (0.15 mg/kg/day), both combined or vehicle with start immediately after the occlusion. After 48 h the rats were sacrificed, the brains sliced and stained with 1% 2, 3, 5-triphenyltetrazolium chloride (TTC) and the volume of ischemic damage determined. The middle cerebral arteries were harvested for immunocytochemical studies of angiotensin AT, and endothelin ETA receptor expression. Candesartan or ZD1611 did alone not significantly decrease the brain damage or improve neurological scores as compared to vehicle controls. The combined inhibition of angiotensin AT, and endothelin ETA receptors however decreased the brain damage and improved the neurological scores (both P &lt; 0.05). The treatment did not change resting mean arterial blood pressure. In addition, there was an upregulation of angiotensin AT, receptors in the ischemic middle cerebral artery smooth muscle cells, which was normalised by the combined treatment. In conclusion, the present study shows that combined inhibition of angiotensin AT, and endothelin ETA receptors reduces the brain damage and improves the neurological outcome after ischemic stroke in rat. (c) 2007 Elsevier B.V. All rights reserved.},
  author       = {Stenman, Emelie and Waldsee, Roya and Henriksson, Marie and Maddahi, Aida and Edvinsson, Lars},
  issn         = {1879-0712},
  keyword      = {angiotensin AT(1) receptor,candesartan,ZD1611,cerebral ischemia,(Rat),endothelin ETA receptor},
  language     = {eng},
  number       = {1-3},
  pages        = {142--148},
  publisher    = {Elsevier},
  series       = {European Journal of Pharmacology},
  title        = {Cooperative effect of angiotensin AT, and endothelin ETA receptor antagonism limits the brain damage after ischemic stroke in rat},
  url          = {http://dx.doi.org/10.1016/j.ejphar.2007.05.049},
  volume       = {570},
  year         = {2007},
}