| 1. |
- Ahnstedt, Hilda, et al.
(författare)
-
Cytokines and growth factors modify the upregulation of contractile endothelin ET(A) and ET(B) receptors in rat cerebral arteries after organ culture.
- 2012
-
Ingår i: Acta Physiologica. - : Wiley. - 1748-1708. ; 205:2, s. 266-278
-
Tidskriftsartikel (refereegranskat)abstract
- Aim: Experimental cerebral ischemia and organ culture of cerebral arteries induce an increased endothelin ET(B) receptor-mediated contraction. The aim of the present study was to examine if cytokines and growth factors, known to be activated in ischemia, can influence the expression and function of endothelin receptors after organ culture. Methods: Rat middle cerebral arteries were cultured for 24 h at 37°C in humidified 5% CO(2) and air in culture medium alone, or with tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), platelet-derived growth factor (PDGF), epidermal growth factor (EGF) or basic fibroblast growth factor (bFGF). Concentration-response curves were obtained for sarafotoxin 6c (ET(B) receptor agonist) and endothelin-1 (here ET(A) receptor agonist, because of ET(B) receptor desensitization). The receptor mRNA expression was examined by real-time PCR and the protein expression by immunohistochemistry and Western blot. Results: TNF-α (100 ng/ml) and EGF (20 ng/ml) potentiated the ET(B) receptor-mediated contraction (increase in pEC(50) without change in E(max) ). bFGF (10 ng/ml) and IL-1β (10 ng/ml) induced an enhanced ET(A) receptor-mediated contraction. bFGF (10 ng/ml) significantly increased the ET(B) mRNA level, and EGF (20 ng/ml) increased the ET(A) receptor protein. Increased ET(B) receptor mRNA and protein level also were observed after treatment with IL-1β (10 ng/ml). Conclusion: The present study show that TNF-α, IL-1β, EGF and bFGF can modify the expression and function of endothelin receptors during organ culture. Since there is similar receptor upregulation in experimental stroke, the effect of cytokines and growth factors on endothelin receptor upregulation is an interesting aspect to study in vivo.
|
|
| 2. |
|
|
| 3. |
|
|
| 4. |
|
|
| 5. |
- Henriksson, Marie, et al.
(författare)
-
MEK1/2 inhibition attenuates vascular ET(A) and ET (B) receptor alterations after cerebral ischaemia.
- 2007
-
Ingår i: Experimental Brain Research. - : Springer Science and Business Media LLC. - 0014-4819 .- 1432-1106. ; 178:4, s. 470-476
-
Tidskriftsartikel (refereegranskat)abstract
- Cerebral ischaemia is associated with elevated levels of endothelin B (ETB) receptors in the ipsilateral middle cerebral artery (MCA). This up-regulation of ET receptors occurs via de novo transcription involving mitogen-activated protein kinases (MAPK). The aim of this study was to examine the effect of inhibition of the MAP kinase/ERK kinase (MEK)1/2 on ET receptor alteration, brain damage, and neurology in experimental cerebral ischaemia. Transient middle cerebral artery occlusion (MCAO) was induced in male Wistar rats by the intraluminal filament technique. The animals received 100 mg/kg intraperitoneally of the MEK1/2 inhibitor U0126 or vehicle in conjunction with the occlusion. After 24 h, the rats were decapitated and the brains removed. The middle cerebral arteries were dissected out and examined with myographs or immunohistochemistry. The ischaemic areas of the brains were compared. After the MCAO, the contractile responses of the ETA and ETB receptors were augmented in the ipsilateral MCA. U0126 decreased this alteration in ET receptor response. Furthermore, treatment with U0126 significantly decreased the brain damage and improved neurological scores. Immunohistochemistry showed that there were lower protein levels of phosphorylated extracellular signal-regulated kinases (ERK)1/2 and phosphorylated transcription factor Elk-1 in the U0126-treated rats compared to control. The results show that treatment with the MEK1/2 inhibitor U0126 in ischaemic stroke decreases brain damage, neurological symptoms, and ET receptor alteration. The vascular effects of U0126 provide new perspective on possible mechanisms of actions of MAPK inhibition in cerebral ischaemia.
|
|
| 6. |
- Henriksson, Marie, et al.
(författare)
-
Protein kinase C inhibition attenuates vascular ETB receptor upregulation and decreases brain damage after cerebral ischemia in rat.
- 2007
-
Ingår i: BMC Neuroscience. - : Springer Science and Business Media LLC. - 1471-2202. ; 8, s. 7-7
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Protein kinase C (PKC) is known to be involved in the pathophysiology of experimental cerebral ischemia. We have previously shown that after transient middle cerebral artery occlusion, there is an upregulation of endothelin receptors in the ipsilateral middle cerebral artery. The present study aimed to examine the effect of the PKC inhibitor Ro-32-0432 on endothelin receptor upregulation, infarct volume and neurology outcome after middle cerebral artery occlusion in rat. Results: At 24 hours after transient middle cerebral artery occlusion (MCAO), the contractile endothelin B receptor mediated response and the endothelin B receptor protein expression were upregulated in the ipsilateral but not the contralateral middle cerebral artery. In Ro-32-0432 treated rats, the upregulated endothelin receptor response was attenuated. Furthermore, Ro-32-0432 treatment decreased the ischemic brain damage significantly and improved neurological scores. Immunohistochemistry showed fainter staining of endothelin B receptor protein in the smooth muscle cells of the ipsilateral middle cerebral artery of Ro-32-0432 treated rats compared to control. Conclusion: The results suggest that treatment with Ro-32-0432 in ischemic stroke decreases the ischemic infarction area, neurological symptoms and associated endothelin B receptor upregulation. This provides a new perspective on possible mechanisms of actions of PKC inhibition in cerebral ischemia.
|
|
| 7. |
|
|
| 8. |
|
|
| 9. |
- Stenman, Emelie, et al.
(författare)
-
Cerebral ischemia upregulates vascular endothelin ETB receptors in rat
- 2002
-
Ingår i: Stroke: a journal of cerebral circulation. - 1524-4628. ; 33:9, s. 2311-2316
-
Tidskriftsartikel (refereegranskat)abstract
- Background and Purpose-Elevated levels of endothelin 1 (ET 1) have been reported in cerebral ischemia A role for ET may prove more important if the vascular receptors were changed We addressed whether there is any change in ET receptor expression in cerebral ischemia Methods-The right middle cerebral artery (MCA) was occluded in male Wistar rats for 2 hours with the intraluminal filament method The basilar artery and both MCAs were removed after 46 hours of recirculation The contractile responses to ET 1 a combined ETA and ETB receptor agonist and sarafotoxin 6c (S6c) a selective ETB receptor agonist were examined in vitro and ET receptor mRNA was quantified by real time polymerase chain reaction Results-S6c which had no contractile effect per se on fresh or sham operated rat cerebral arteries induced a marked contraction in the occluded MCA (E-m [maximum contraction calculated as percentage of the contractile capacity of 63 5 mmol/L K+] =68+/-68% P<0 0001) while there was no difference in the responses to ET 1 after cerebral ischemia Real time polymerase chain reaction revealed a significant upregulation of both the ETA and ETB receptors (both P<0 05) in the occluded MCA compared with the nonoccluded MCA from the same rats Conclusions-Focal cerebral ischemia in rat induces increased transcription of both ETA and ETB receptors which results in the appearance of a contractile response to the ETB receptor agonist S6c These results suggest a role for ET receptors in the pathogenesis of a vascular component after cerebral ischemia.
|
|
| 10. |
- Stenman, Emelie, et al.
(författare)
-
Cooperative effect of angiotensin AT, and endothelin ETA receptor antagonism limits the brain damage after ischemic stroke in rat
- 2007
-
Ingår i: European Journal of Pharmacology. - : Elsevier BV. - 1879-0712 .- 0014-2999. ; 570:1-3, s. 142-148
-
Tidskriftsartikel (refereegranskat)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 < 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.
|
|
