title: Vasorelaxant effects of Shunaoxin pill are mediated by NO/cGMP pathway, HO/CO pathway and calcium channel blockade in isolated rat thoracic aorta.
abstract: BACKGROUND
  Shunaoxin pill (SNX), one of the famous classical recipes in traditional Chinese medicine, is developed from the "Decoction of Xionggui". It has been used for treatment of cerebrovascular related diseases. It is well known that vasodilatation plays a very important role in cerebrovascular diseases. The effect of SNX on vasorelaxant activity has not yet been explored. Therefore, we aimed to investigate the vasorelaxant effects of SNX on isolated rat thoracic aorta so as to assess some of the possible mechanisms. We also investigate the gasotransmitter signaling pathway involved which has been rarely reported in isolated rat thoracic aorta before.
  
  
  OBJECTIVE
  The present study was performed to examine the vasodilative activity of SNX and its mechanisms in isolated rat thoracic aorta.
  
  
  METHODS
  SNX was studied on isolated rat thoracic aorta in vitro, including endothelium-intact and endothelium-denuded aortic rings. In present study, specific inhibitors including soluble guanylate cyclase (sGC) inhibitor 1 H-[1,2,4]oxadiazolo[4,3-a]quinoxaline-1-one (ODQ), cyclooxygenase (COX) inhibitor indomethacin (INDO), NO synthase inhibitor NG-nitro-l-arginine methyl ester (L-NAME), heme oxygenase-1 (HO-1) inhibitor zinc-protoporphyrin (ZnPP), cystathionine γ-lyase (CSE) inhibitor DL-Propargylglycine (PAG), non-selective K(+) channel inhibitor tetraethylammonium chloride (TEA), KV channel inhibitor 4-Aminopyridine (4-AP), and KATP channel inhibitor Glibenclamide (Gli) were used, they were added 20min before NE contraction and then added SNX to induce vasodilation.
  
  
  RESULTS
  Removal of endothelium or pretreatment of aortic rings (intact endothelium) with L-NAME, ODQ or ZnPP significantly blocked SNX-induced relaxation. Pretreatment with the non-selective K(+) channel inhibitor TEA, KV channel inhibitor 4-AP or the KATP channel inhibitor Gli, none of them had influences on the SNX-induced response (p>0.05). Besides, SNX inhibited the contraction triggered by NE in endothelium-denuded rings in Ca(2+)-free medium. SNX also produced rightward parallel displacement of CaCl2 curves.
  
  
  CONCLUSIONS
  These results suggest that SNX can induce less endothelium-dependent and more endothelium-independent vascular relaxation. The NO/cGMP and HO/CO pathways, blockade of Ca(2+) channels are inhibition of IP3R mediated Ca(2+) mobilization from intracellular stores, are likely involved in this relaxation. Furthermore, the underlying mechanisms of combined compositions in SNX await further investigations.
authors.affiliation: School of Pharmaceutical Science and Technology, Tianjin University, Weijin Road, Tianjin 300072, China.
authors.forename: Liqin
authors.initials: L
authors.lastname: Huo
authors.affiliation: Tianjin Key Laboratory of Cardiovascular Remodeling and Target Organ Injury, Logistics College of Chinese People's Armed Police Forces, Tianjin 300162, China; Department of Pharmacy, Logistics College of Chinese People's Armed Police Forces, Tianjin 300162, China.
authors.forename: Jingze
authors.initials: J
authors.lastname: Zhang
authors.affiliation: School of Pharmaceutical Science and Technology, Tianjin University, Weijin Road, Tianjin 300072, China.
authors.forename: Zhuo
authors.initials: Z
authors.lastname: Qu
authors.affiliation: Department of Pharmacy, Logistics College of Chinese People's Armed Police Forces, Tianjin 300162, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Chen
authors.affiliation: Tianjin Key Laboratory of Cardiovascular Remodeling and Target Organ Injury, Logistics College of Chinese People's Armed Police Forces, Tianjin 300162, China.
authors.forename: Yuming
authors.initials: Y
authors.lastname: Li
authors.affiliation: School of Pharmaceutical Science and Technology, Tianjin University, Weijin Road, Tianjin 300072, China. Electronic address: pharmgao@tju.edu.cn.
authors.forename: Wenyuan
authors.initials: W
authors.lastname: Gao
mesh_terms: D015107:4-Butyrolactone / Q000031:analogs & derivatives / Q000032:analysis; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D002118:Calcium / Q000502:physiology; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D015220:Calcium Channels / Q000378:metabolism; D002248:Carbon Monoxide / Q000378:metabolism; D003373:Coumaric Acids / Q000032:analysis; D006152:Cyclic GMP / Q000378:metabolism; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D009638:Norepinephrine; D011189:Potassium Chloride; D017208:Rats, Wistar; D013607:Tablets; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: D002121:Calcium Channel Blockers; D015220:Calcium Channels; D003373:Coumaric Acids; D004365:Drugs, Chinese Herbal; D013607:Tablets; D014665:Vasodilator Agents; C000591859:shunaoxin; D009569:Nitric Oxide; C027820:ligustilide; D011189:Potassium Chloride; D002248:Carbon Monoxide; C004999:ferulic acid; D006419:Heme Oxygenase (Decyclizing); D006152:Cyclic GMP; D015107:4-Butyrolactone; D002118:Calcium; D009638:Norepinephrine
keywords: Aortic rings; Carbon monoxide; Ferulic acid (PubChem CID: 445858); Gasotransmitter; Hydrogen sulfide; Levistolide A (PubChem CID: 70698035); Ligustilide (PubChem CID: 53190221); Nitric oxide; Senkyunolide A (PubChem CID: 3085257); Senkyunolide H (PubChem CID: 5321251); Senkyunolide I (PubChem CID: 11521428); Vasorelaxation