title: Magnesium lithospermate B, an active extract of Salvia miltiorrhiza, mediates sGC/cGMP/PKG translocation in experimental vasospasm.
abstract: BACKGROUND
  Soluble guanylyl cyclases (sGCs) and Ras homolog gene family, member A (rhoA)/Ras homolog gene family kinase(rho-kinase) plays a role in vascular smooth muscle relaxation in subarachnoid hemorrhage (SAH). It is of interest to examine the effect of MLB on rhoA/ROCK and sGC/cGMP/PKG expression.
  
  
  METHODS
  A rodent SAH model was employed. Tissue samples were for sGC α 1, sGC β 1, PKG, rhoA, ROCK (Western blot), and cGMP (ELISA) measurement.
  
  
  RESULTS
  MLB morphologically improved convolution of the internal elastic lamina, distortion of endothelial wall, and necrosis of the smooth muscle in the SAH rats. Expressed cGMP, sGC α 1, sGC β 1, and PKG in the SAH groups were reduced (P < 0.01), and MLB precondition significantly induced cGMP, sGCα1, sGCβ1, and PKG. L-NAME reversed the vasodilation effect of MLB, reduced the bioexpression of PKG and cGMP (P < 0.01), and tends to reduce sGCα1 level and induce rhoA, ROCK level in MLB precondition + SAH groups.
  
  
  CONCLUSIONS
  These results demonstrate that sGC/cGMP/PKG and NO/ET pathways play pivotal roles in SAH-induced vasospasm. Through activating sGC/cGMP/PKG pathway and partially by inactivating rho-kinase in a NO-dependent mechanism, MLB shows promise to be an effective strategy for the treatment of this disease entity.
authors.affiliation: Department of Surgery, Faculty of Medicine, School of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan ; Department of Neurosurgery, Kaohsiung Medical University Hospital, No. 100, Tzyou 1st Road, Kaohsiung 80752, Taiwan ; Department of Surgery, Kaohsiung Municipal Ta Tung Hospital, Kaohsiung, Taiwan.
authors.forename: Chih-Zen
authors.initials: CZ
authors.lastname: Chang
authors.affiliation: Department of Neurosurgery, Kaohsiung Medical University Hospital, No. 100, Tzyou 1st Road, Kaohsiung 80752, Taiwan.
authors.forename: Shu-Chuan
authors.initials: SC
authors.lastname: Wu
authors.affiliation: Department of Surgery, Faculty of Medicine, School of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan ; Department of Neurosurgery, Kaohsiung Medical University Hospital, No. 100, Tzyou 1st Road, Kaohsiung 80752, Taiwan.
authors.forename: Aij-Lie
authors.initials: AL
authors.lastname: Kwan
mesh_terms: D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D001892:Camphanes; D006152:Cyclic GMP / Q000378:metabolism*; D017869:Cyclic GMP-Dependent Protein Kinases / Q000378:metabolism*; D004195:Disease Models, Animal; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000494:pharmacology*; D006162:Guanylate Cyclase / Q000378:metabolism*; D008297:Male; D053723:Panax notoginseng; D051381:Rats; D017207:Rats, Sprague-Dawley; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D027561:Salvia miltiorrhiza / Q000737:chemistry*; D015398:Signal Transduction / Q000187:drug effects; D000071756:Soluble Guanylyl Cyclase; D020301:Vasospasm, Intracranial / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology
chemical_list: D001892:Camphanes; D004365:Drugs, Chinese Herbal; D018160:Receptors, Cytoplasmic and Nuclear; C000604051:danshen dripping pill; C061091:lithospermate B; D017869:Cyclic GMP-Dependent Protein Kinases; D006162:Guanylate Cyclase; D000071756:Soluble Guanylyl Cyclase; D006152:Cyclic GMP