Magnesium lithospermate B alleviates the production of endothelin-1 through an NO-dependent mechanism and reduces experimental vasospasm in rats
- نوع فایل : کتاب
- زبان : انگلیسی
- مؤلف : Chih-Zen Chang & Shu-Chuan Wu & Aij-Lie Kwan & Shi-Lin Hwang & Shen-Long Howng
- چاپ و سال / کشور: 2011
Description
Objective Magnesium lithospermate B (MLB), a working extract from Salvia miltiorrhiza, was effective against coronary artery disease, ischemic stroke, and chronic renal disease. This study examined the effect of MLB on endothelin-1/endothelial nitric oxide synthase (eNOS) in a subarachnoid hemorrhage (SAH) animal model. Methods A rodent double-hemorrhage model was employed. Animals were randomly assigned to five groups (sham, SAH only, vehicle, 10 mg/kg/day MLB treatment, and pretreatment groups). A radiolabeled NOS Assay Kit was used to detect eNOS. Serum and cerebrospinal fluid sampling for ET-1 (ELISA) was measured. The basilar arteries (BAs) were garnered and sliced, and their crosssectional areas were determined. In addition, NOS inhibitor nitro-arginine methyl ester (L-NAME) was employed in the SAH+ MLB treatment groups. Results Significant vasoconstriction was perceived in the SAH group (lumen patency: 44.6%, p<0.01), but not in the MLB group (lumen patency: 89.3%). The ET-1 level was reduced in the MLP plus SAH group (34%, p<0.01) when compared with the SAH groups (SAH only and vehicle). MLB dose-dependently increased the level of eNOS when compared with the vehicle plus SAH group. However, the administration of L-NAME reversed the expression of eNOS and vasoconstriction (lumen patency: 56.2%) in the MLB group. Conclusion The enhanced expression of eNOS and decreased ET-1 levels in the MLB groups may reflect its anti-spastic effect. In the study of NOS, L-NAME reversed MLB’s anti-vasospastic effect. This finding lends credence to the hypothesis that MLB modulates ET-1 levels through a NOS-dependent mechanism in the pathogenesis of cerebral vasospasm following SAH.
Acta Neurochir DOI 10.1007/s00701-011-1082-6 received: 12 April 2011 / Accepted: 22 June 2011
