title: Mechanisms underlying the cardioprotective effect of Salvianic acid A against isoproterenol-induced myocardial ischemia injury in rats: Possible involvement of L-type calcium channels and myocardial contractility.
abstract: BACKGROUND
  Salvianic acid A (SAA), which is the main water-soluble fraction in Radix Salviae Milthiorrhizae, has been widely applied for treating cardiovascular diseases in China.
  
  
  OBJECTIVE
  To explore the effects of SAA against myocardial ischemia injury induced by isoproterenol (ISO) in rats and to clarify its underlying myocardial protective mechanisms based on l-type calcium channels and myocardial contractility.
  
  
  METHODS
  The myocardial ischemia injured rat model was induced by administering ISO (85mg/kg) subcutaneously at evenly spaced intervals throughout the day and night for 2 consecutive days. Serum cardiac biomarkers were analyzed, and heart tissues were isolated and prepared for histopathology assay. The regulatory effects of SAA on the L-type calcium current (ICa-L) in rat ventricular myocytes were observed by the patch clamp technique. The IonOptix Myocam detection system was used to observe the contractility of isolated rat ventricular myocytes.
  
  
  RESULTS
  SAA significantly ameliorated changes in heart morphology and electrocardiographic patterns and reduced serum levels of creatine kinase and lactate dehydrogenase in the ISO-induced myocardial ischemia injured rat model. Meanwhile, SAA reduced ICa-L in a concentration-time dependent way with an IC50 of 1.47×10(-5)M, upshifted the current-voltage, activation, and inactivation curves of ICa-L, and significantly inhibited the amplitude of the cell shortening.
  
  
  CONCLUSIONS
  These results indicate that SAA exhibits significant cardioprotective effects against the ISO-induced myocardial ischemia injury, potentially through inhibiting ICa-L and decreasing myocardial contractility.
authors.affiliation: Hebei Medical University, No.361, East Zhongshan Road, Shijiazhuang 050017, Hebei, China.
authors.forename: Qiongtao
authors.initials: Q
authors.lastname: Song
authors.affiliation: The Fourth Hospital of Hebei Medical University, No.12, Jiankang Road, Shijiazhuang 050011, Hebei, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Chu
authors.affiliation: Hebei University of Chinese Medicine, No.3, Xingyuan Road, Shijiazhuang 050200, Hebei, China.
authors.forename: Xuan
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Drug Metabolism & Pharmacokinetics, China Pharmaceutical University, No. 1, Shennong Road of the Central Door, Nanjing 210038, Jiangsu, China.
authors.forename: Yifan
authors.initials: Y
authors.lastname: Bao
authors.affiliation: Hebei University of Chinese Medicine, No.3, Xingyuan Road, Shijiazhuang 050200, Hebei, China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Hebei University of Chinese Medicine, No.3, Xingyuan Road, Shijiazhuang 050200, Hebei, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Guo
authors.affiliation: Hebei Medical University, No.361, East Zhongshan Road, Shijiazhuang 050017, Hebei, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Infectious Diseases, Hebei General Hospital, Shijiazhuang, Hebei 050051, China.
authors.forename: Hongying
authors.initials: H
authors.lastname: Liu
authors.affiliation: Hebei University of Chinese Medicine, No.3, Xingyuan Road, Shijiazhuang 050200, Hebei, China.
authors.forename: Jianping
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Hebei University of Chinese Medicine, No.3, Xingyuan Road, Shijiazhuang 050200, Hebei, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Hebei Medical University, No.361, East Zhongshan Road, Shijiazhuang 050017, Hebei, China; Hebei University of Chinese Medicine, No.3, Xingyuan Road, Shijiazhuang 050200, Hebei, China. Electronic address: chuli0614@126.com.
authors.forename: Li
authors.initials: L
authors.lastname: Chu
mesh_terms: D000200:Action Potentials; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D020746:Calcium Channels, L-Type / Q000187:drug effects* / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects; D003402:Creatine Kinase / Q000097:blood; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D004562:Electrocardiography; D007545:Isoproterenol; D007770:L-Lactate Dehydrogenase / Q000097:blood; D007773:Lactates / Q000494:pharmacology*; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D009203:Myocardial Infarction / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D018408:Patch-Clamp Techniques; D017207:Rats, Sprague-Dawley; D013997:Time Factors
chemical_list: D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D004365:Drugs, Chinese Herbal; D007773:Lactates; C035055:3,4-dihydroxyphenyllactic acid; D007770:L-Lactate Dehydrogenase; D003402:Creatine Kinase; D007545:Isoproterenol
keywords: Isoproterenol; L-type calcium current; Myocardial contractility; Myocardial ischemia injury; Radix Salviae Milthiorrhizae; Salvianic acid A