Protective mechanisms of the angiotensin II type 1 receptor blocker candesartan against cerebral ischemia : in-vivo and in-vitro studies
BACKGROUND: Angiotensin II type 1 (AT1) receptor blockers decrease ischemia by mechanisms dependent on and independent of arterial blood pressure in hypertensive rats and AT1-R knockout mice, respectively. However, the detailed mechanisms underlying the effects of AT1 receptor blockers remain unclear.
AIMS: To elucidate the systemic and focal effects of AT1 receptor blockers against cerebral ischemia in in-vivo and in-vitro studies.
METHODS: Normotensive Wistar rats were treated for 2 weeks with 0.5 or 1 mg/kg candesartan cilexetil and then subjected to 2-h middle cerebral artery occlusion-reperfusion. Human umbilical endothelial cells were stimulated with the active form of candesartan and angiotensin II in the absence and presence of an angiotensin II type 2 (AT2) receptor antagonist.
RESULTS: In candesartan-pretreated hypotensive and nonhypotensive rats, blood pressure was moderately increased during middle cerebral artery occlusion and fell gradually to the baseline after the reperfusion; it remained elevated in the control even after the reperfusion occlusion. Candesartan treatment resulted in a decrease in the cortical infarct volume and oxidative damage, the hypoxic status was improved, and the expression of repair-associated and growth-associated proteins in the cortical penumbra was augmented. Candesartan also increased the eNOS mRNA level and the lumen size of the middle cerebral artery. In human umbilical endothelial cells, candesartan increased the eNOS protein level AT2-R dependently, inhibited the expression of nicotinamide adenine dinucleotide phosphate oxidase subunits and angiotensin II-induced intracellular reactive oxygen species and nitric oxide, and promoted the extracellular release of nitric oxide, suggesting that it augmented the bioavailability of nitric oxide.
CONCLUSION: Among the mechanisms candesartan exerts in its protection against cerebral ischemia, restoration of endothelial function may represent an attractive therapeutic goal to address cerebral ischemia.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2008 |
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| Erschienen: |
2008 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:26 |
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| Enthalten in: |
Journal of hypertension - 26(2008), 7 vom: 01. Juli, Seite 1435-45 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Liu, Hao [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 23.10.2008 Date Revised 18.03.2022 published: Print Citation Status MEDLINE |
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| doi: |
10.1097/HJH.0b013e3283013b6e |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM180186620 |
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| 100 | 1 | |a Liu, Hao |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Protective mechanisms of the angiotensin II type 1 receptor blocker candesartan against cerebral ischemia |b in-vivo and in-vitro studies |
| 264 | 1 | |c 2008 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 23.10.2008 | ||
| 500 | |a Date Revised 18.03.2022 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a BACKGROUND: Angiotensin II type 1 (AT1) receptor blockers decrease ischemia by mechanisms dependent on and independent of arterial blood pressure in hypertensive rats and AT1-R knockout mice, respectively. However, the detailed mechanisms underlying the effects of AT1 receptor blockers remain unclear | ||
| 520 | |a AIMS: To elucidate the systemic and focal effects of AT1 receptor blockers against cerebral ischemia in in-vivo and in-vitro studies | ||
| 520 | |a METHODS: Normotensive Wistar rats were treated for 2 weeks with 0.5 or 1 mg/kg candesartan cilexetil and then subjected to 2-h middle cerebral artery occlusion-reperfusion. Human umbilical endothelial cells were stimulated with the active form of candesartan and angiotensin II in the absence and presence of an angiotensin II type 2 (AT2) receptor antagonist | ||
| 520 | |a RESULTS: In candesartan-pretreated hypotensive and nonhypotensive rats, blood pressure was moderately increased during middle cerebral artery occlusion and fell gradually to the baseline after the reperfusion; it remained elevated in the control even after the reperfusion occlusion. Candesartan treatment resulted in a decrease in the cortical infarct volume and oxidative damage, the hypoxic status was improved, and the expression of repair-associated and growth-associated proteins in the cortical penumbra was augmented. Candesartan also increased the eNOS mRNA level and the lumen size of the middle cerebral artery. In human umbilical endothelial cells, candesartan increased the eNOS protein level AT2-R dependently, inhibited the expression of nicotinamide adenine dinucleotide phosphate oxidase subunits and angiotensin II-induced intracellular reactive oxygen species and nitric oxide, and promoted the extracellular release of nitric oxide, suggesting that it augmented the bioavailability of nitric oxide | ||
| 520 | |a CONCLUSION: Among the mechanisms candesartan exerts in its protection against cerebral ischemia, restoration of endothelial function may represent an attractive therapeutic goal to address cerebral ischemia | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 7 | |a Angiotensin II Type 1 Receptor Blockers |2 NLM | |
| 650 | 7 | |a Benzimidazoles |2 NLM | |
| 650 | 7 | |a Biphenyl Compounds |2 NLM | |
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| 650 | 7 | |a candesartan cilexetil |2 NLM | |
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| 700 | 1 | |a Kitazato, Keiko T |e verfasserin |4 aut | |
| 700 | 1 | |a Uno, Masaaki |e verfasserin |4 aut | |
| 700 | 1 | |a Yagi, Kenji |e verfasserin |4 aut | |
| 700 | 1 | |a Kanematsu, Yasuhisa |e verfasserin |4 aut | |
| 700 | 1 | |a Tamura, Tetsuya |e verfasserin |4 aut | |
| 700 | 1 | |a Tada, Yoshiteru |e verfasserin |4 aut | |
| 700 | 1 | |a Kinouchi, Tomoya |e verfasserin |4 aut | |
| 700 | 1 | |a Nagahiro, Shinji |e verfasserin |4 aut | |
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