Tanshinone IIA protects against chronic intermittent hypoxia-induced myocardial injury via activating the endothelin 1 pathway

Biomed Pharmacother. 2017 Nov:95:1013-1020. doi: 10.1016/j.biopha.2017.08.036. Epub 2017 Sep 13.

Abstract

Tanshinone IIA (Tan IIA) may exert significant protective effects against heart oxidative stress damage in obstructive sleep apnoea (OSA) syndrome. Chronic intermittent hypoxia (CIH)-triggered left ventricular dysfunction is used in a rat model to mimic CIH in OSA patients. 48 rats were randomly divided into three groups: normal control (NC) group, CIH group and CIH+Tan IIA group with 16 rats in each group. At the end of experiment (day 21), the blood pressure, Plasma ET-1 and NO content, hemodynamic indexes, heart histology, myocardial apoptosis as well as the expression of eNOS, ET-1, ETA receptor and ETB receptor were compared among different groups. Tan IIA was able to inhibit the increase of blood pressure induced by CIH. Meanwhile, rat cardiac function in Tan IIA group was evaluated by hemodynamic indexes, histopathological examination. Higher ventricular eNOS activity was induced by Tan IIA with a reduction in both ET-1 and ETA receptor expression. However, Tan IIA largely inhibited the decrease of ETB receptor expression. This study demonstrated that Tan IIA has the potential to benefit rat heart against CIH via endothelin system.

Keywords: Chronic intermittent hypoxia; Endothelin; Myocardial injury; Tanshinone IIA.

MeSH terms

  • Abietanes / pharmacology
  • Abietanes / therapeutic use*
  • Animals
  • Apoptosis / drug effects
  • Blood Pressure / drug effects
  • Cardiotonic Agents / pharmacology
  • Cardiotonic Agents / therapeutic use*
  • Chronic Disease
  • Electrocardiography
  • Endothelin-1 / metabolism*
  • Heart Function Tests / drug effects
  • Hemodynamics / drug effects
  • Hypoxia / blood
  • Hypoxia / drug therapy*
  • Hypoxia / pathology*
  • Hypoxia / physiopathology
  • Male
  • Myocardium / metabolism*
  • Myocardium / pathology*
  • Myocytes, Cardiac / drug effects
  • Myocytes, Cardiac / metabolism
  • Myocytes, Cardiac / pathology
  • Nitric Oxide / blood
  • Nitric Oxide Synthase Type III / metabolism
  • Rats, Sprague-Dawley
  • Receptor, Endothelin A / metabolism
  • Receptor, Endothelin B / metabolism
  • Signal Transduction*
  • Systole / drug effects

Substances

  • Abietanes
  • Cardiotonic Agents
  • Endothelin-1
  • Receptor, Endothelin A
  • Receptor, Endothelin B
  • tanshinone
  • Nitric Oxide
  • Nitric Oxide Synthase Type III