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

J Ethnopharmacol. 2016 Aug 2:189:157-64. doi: 10.1016/j.jep.2016.05.038. Epub 2016 May 20.

Abstract

Ethnopharmacological relevance: 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.

Aim of the study: 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.

Materials and 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.

Keywords: Isoproterenol; L-type calcium current; Myocardial contractility; Myocardial ischemia injury; Radix Salviae Milthiorrhizae; Salvianic acid A.

MeSH terms

  • Action Potentials
  • Animals
  • Calcium Channel Blockers / pharmacology*
  • Calcium Channels, L-Type / drug effects*
  • Calcium Channels, L-Type / metabolism
  • Calcium Signaling / drug effects
  • Creatine Kinase / blood
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Drugs, Chinese Herbal / pharmacology*
  • Electrocardiography
  • Isoproterenol*
  • L-Lactate Dehydrogenase / blood
  • Lactates / pharmacology*
  • Male
  • Myocardial Contraction / drug effects*
  • Myocardial Infarction / chemically induced
  • Myocardial Infarction / metabolism
  • Myocardial Infarction / physiopathology
  • Myocardial Infarction / prevention & control*
  • Myocardium / metabolism*
  • Myocardium / pathology
  • Patch-Clamp Techniques
  • Rats, Sprague-Dawley
  • Time Factors

Substances

  • Calcium Channel Blockers
  • Calcium Channels, L-Type
  • Drugs, Chinese Herbal
  • Lactates
  • 3,4-dihydroxyphenyllactic acid
  • L-Lactate Dehydrogenase
  • Creatine Kinase
  • Isoproterenol