Simvastatin re-couples dysfunctional endothelial nitric oxide synthase in experimental subarachnoid hemorrhage.
Reduced endothelial nitric oxide synthase (eNOS) function has been linked to secondary complications of subarachnoid hemorrhage (SAH). We previously found that there is increased eNOS function after SAH but that it is uncoupled, leading to secondary complications such as vasospasm, microthromboembol...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2011-01-01
|
| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3044158?pdf=render |
| _version_ | 1819161988355325952 |
|---|---|
| author | Mohammed Sabri Jinglu Ai Philip A Marsden R Loch Macdonald |
| author_facet | Mohammed Sabri Jinglu Ai Philip A Marsden R Loch Macdonald |
| author_sort | Mohammed Sabri |
| collection | DOAJ |
| description | Reduced endothelial nitric oxide synthase (eNOS) function has been linked to secondary complications of subarachnoid hemorrhage (SAH). We previously found that there is increased eNOS function after SAH but that it is uncoupled, leading to secondary complications such as vasospasm, microthromboembolism and neuronal apoptosis. Here we test the hypothesis that recoupling eNOS with simvastatin can prevent these complications. SAH was created in mice that were treated with vehicle or simvastatin starting 2 weeks before or 30 minutes after SAH. SAH increased phosphorylated eNOS which was prevented by pre- or post-treatment with simvastatin. Simvastatin pre-treatment also prevented the increase in eNOS monomer formation that was associated with SAH, decreased superoxide anion radical production and increased NO. These changes were associated with decreased vasospasm, microthromboemboli and neuronal injury. The data suggest that simvastatin re-couples eNOS after SAH, leading to decreased secondary complications such as vasospasm, microthromboemboli and neuronal injury. |
| first_indexed | 2024-12-22T17:21:05Z |
| format | Article |
| id | doaj.art-47efc34703eb4ea085199a97a335ced6 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-22T17:21:05Z |
| publishDate | 2011-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-47efc34703eb4ea085199a97a335ced62022-12-21T18:18:49ZengPublic Library of Science (PLoS)PLoS ONE1932-62032011-01-0162e1706210.1371/journal.pone.0017062Simvastatin re-couples dysfunctional endothelial nitric oxide synthase in experimental subarachnoid hemorrhage.Mohammed SabriJinglu AiPhilip A MarsdenR Loch MacdonaldReduced endothelial nitric oxide synthase (eNOS) function has been linked to secondary complications of subarachnoid hemorrhage (SAH). We previously found that there is increased eNOS function after SAH but that it is uncoupled, leading to secondary complications such as vasospasm, microthromboembolism and neuronal apoptosis. Here we test the hypothesis that recoupling eNOS with simvastatin can prevent these complications. SAH was created in mice that were treated with vehicle or simvastatin starting 2 weeks before or 30 minutes after SAH. SAH increased phosphorylated eNOS which was prevented by pre- or post-treatment with simvastatin. Simvastatin pre-treatment also prevented the increase in eNOS monomer formation that was associated with SAH, decreased superoxide anion radical production and increased NO. These changes were associated with decreased vasospasm, microthromboemboli and neuronal injury. The data suggest that simvastatin re-couples eNOS after SAH, leading to decreased secondary complications such as vasospasm, microthromboemboli and neuronal injury.http://europepmc.org/articles/PMC3044158?pdf=render |
| spellingShingle | Mohammed Sabri Jinglu Ai Philip A Marsden R Loch Macdonald Simvastatin re-couples dysfunctional endothelial nitric oxide synthase in experimental subarachnoid hemorrhage. PLoS ONE |
| title | Simvastatin re-couples dysfunctional endothelial nitric oxide synthase in experimental subarachnoid hemorrhage. |
| title_full | Simvastatin re-couples dysfunctional endothelial nitric oxide synthase in experimental subarachnoid hemorrhage. |
| title_fullStr | Simvastatin re-couples dysfunctional endothelial nitric oxide synthase in experimental subarachnoid hemorrhage. |
| title_full_unstemmed | Simvastatin re-couples dysfunctional endothelial nitric oxide synthase in experimental subarachnoid hemorrhage. |
| title_short | Simvastatin re-couples dysfunctional endothelial nitric oxide synthase in experimental subarachnoid hemorrhage. |
| title_sort | simvastatin re couples dysfunctional endothelial nitric oxide synthase in experimental subarachnoid hemorrhage |
| url | http://europepmc.org/articles/PMC3044158?pdf=render |
| work_keys_str_mv | AT mohammedsabri simvastatinrecouplesdysfunctionalendothelialnitricoxidesynthaseinexperimentalsubarachnoidhemorrhage AT jingluai simvastatinrecouplesdysfunctionalendothelialnitricoxidesynthaseinexperimentalsubarachnoidhemorrhage AT philipamarsden simvastatinrecouplesdysfunctionalendothelialnitricoxidesynthaseinexperimentalsubarachnoidhemorrhage AT rlochmacdonald simvastatinrecouplesdysfunctionalendothelialnitricoxidesynthaseinexperimentalsubarachnoidhemorrhage |