Article
The family of methylated L-arginines (L-NMMA, ADMA and SDMA) : endogenous nitric oxide synthase inhibitors and their role in the pathogenesis of cerebral vasospasm in vitro and in vivo
Die Familie der methylierten L-Arginine (L-NMMA, ADMA and SDMA): endogene NO-Synthetase Inhibitoren und ihre Rolle in der Pathogenese des zerebralen Vasospasmus
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Authors
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C. S. Jung
- Neurochirurgische Klinik, Johann-Wolfgang-Goethe-Universität, Frankfurt am Main
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R. M. Pluta
- Surgical Neurology Branch, NINDS, NIH, Bethesda, USA
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E. H. Oldfield
- Surgical Neurology Branch, NINDS, NIH, Bethesda, USA
| Published: | May 4, 2005 |
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Outline
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Objective
Endothelial dysfunction was observed in cerebral vasospasm after subarachnoid hemorrhage (SAH). Monomethyl-L-arginine (L-NMMA), asymmetric- and symmetric dimethyl-L-arginine (ADMA, SDMA) are produced by endothelial cells. They can inhibit endothelial nitric oxide synthase and produce endothelial dysfunction. Subarachnoid hemorrhage may evoke production and release of methylated arginines. We sought to determine L-NMMA, ADMA and SDMA level in vitro and in vivo and elucidate their role in cerebral vasospasm after SAH.
Methods
L-NMMA, ADMA, SDMA and NO metabolite levels were determined in CSF and serum samples from 30 patients and 22 animals after SAH as well as in human endothelial cell cultures treated with blood derived spasmogens.
Results
ADMA levels remained unchanged in patients and animals without vasospasm, but significantly increased during vasospasm: (6.2mM±1.7mM and 2.8mM±1.9mM vs. 15.7±6.3mM and 7.2mM±1.9mM;p<0.001) and decreased with resolution of vasospasm. Levels of L-NMMA and SDMA showed no significant alterations during vasospasm. ADMA levels were correlated with the degree of vasospasm (cc=0.82;p<0.0001) and negatively correlated with NO metabolite levels (cc=-0.32;p=0.008;cc=-0.25; p=0.04). ADMA increased after treatment with blood derived spasmogens from 7pM±3.7 to 12,3±3.7pM/mg Protein.
Conclusions
Blood derived spasmogens lead to increased levels of methylated arginines in vitro. ADMA levels significantly increased during vasospasm and were correlated with cerebral vasospasm and NO metabolite levels. Thus, the family of methylated arginines, especially ADMA, seem to be involved in the development of cerebral vasospasm.
