title: Magnesium lithospermate B alleviates the production of endothelin-1 through an NO-dependent mechanism and reduces experimental vasospasm in rats.
abstract: 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 cross-sectional 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Surgery, College of Medicine, Kaohsiung Medical University, Taiwan, Republic of China. cjc4b@pchome.com.tw
authors.forename: Chih-Zen
authors.initials: CZ
authors.lastname: Chang
authors.forename: Shu-Chuan
authors.initials: SC
authors.lastname: Wu
authors.forename: Aij-Lie
authors.initials: AL
authors.lastname: Kwan
authors.forename: Shi-Lin
authors.initials: SL
authors.lastname: Hwang
authors.forename: Shen-Long
authors.initials: SL
authors.lastname: Howng
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004365:Drugs, Chinese Herbal / Q000494:pharmacology* / Q000627:therapeutic use; D019332:Endothelin-1 / Q000096:biosynthesis*; D016166:Free Radical Scavengers / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D009569:Nitric Oxide / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013345:Subarachnoid Hemorrhage / Q000150:complications / Q000503:physiopathology*; D020301:Vasospasm, Intracranial / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology
chemical_list: D004365:Drugs, Chinese Herbal; D019332:Endothelin-1; D016166:Free Radical Scavengers; C061091:lithospermate B; D009569:Nitric Oxide