Correlation between asymmetric dimethylarginine and cerebral vasospasm secondary to subarachnoid hemorrhage

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Objective To investigate the correlation between asymmetric dimethylarginine (ADMA) and cerebral vasospasm (CVS) secondary to subarachnoid hemorrhage (SAH).Methods Seventy-eight healthy male adult Sprague-Dawley rats were randomly allocated into control group (n =6),sham group (n =36) and SAH group (n =36).In SAH group,a SAH model was established by double autologous blood injection into cisterna magna.Arterial blood,cerebrospinal fluid (CSF) and basilar artery samples of each group were collected at the preconcerted time.ADMA levels in the plasma and CSF samples were assessed using enzyme-linked immuno sorbent assay (ELISA).Nitrite and nitrate concentrations were used as a marker of nitric oxide production in plasma and CSF samples and determined by using nitrate reductase method.Pathomorphological changes were observed with optical microscope and inner diameter of basilar artery was measured by Micrometer after hematoxylin-eosin staining was performed.Results (1) In SAH group,ADMA levels in CSF samples were significantly increased at 1st,3rd,5th and 7th day (P ＜0.05),and NO levels in CSF samples were significantly decreased at 3rd,5th,and 7th day as compared with sham group (P＜0.01).(2) The ratio of thickness and inner diameter of basilar artery was used to indicate the degree of CVS.The level of ADMA in CSF samples was strongly correlated with the degree of CVS (r =0.641,P ＜0.01).Nitrite levels in CSF samples were negatively correlated with ADMA levels in CSF samples (r =-0.687,P ＜0.01).(3) Plasma ADMA levels in sham group and SAH group were similar and remained essentially unchanged during the several days after SAH.Plasma ADMA levels were neither correlated with NO levels (r =0.019,P ＞ 0.05) nor with the degree of vasospasm (r =-0.046,P ＞ 0.05).Conclusion Asymmetric dimethylarginine reduces the level of nitric oxide in CSF by inhibiting nitric oxide synthase and may be involved in the progression of cerebral vasospasm.The level of ADMA in CSF samples was strongly correlated with the degree of CVS in SAH rats.There is no evident correlation between the level of ADMA in plasma and the degree of CVS. Key words: Subarachnoid hemorrhage; Cerebral vasospasm ; Asymmetric dimethylarginine ; Nitric oxide