Echinacoside prevents hypoxic pulmonary hypertension by regulating the pulmonary artery function

J Pharmacol Sci. 2020 Dec;144(4):237-244. doi: 10.1016/j.jphs.2020.09.002. Epub 2020 Sep 10.

Abstract

Hypoxic pulmonary hypertension (HPH) is a progressive and irreversible disease that reduces survival. Echinacoside is a phenylethanoid glycoside from Tibetan herbs known for its vasorelaxant effect and for inhibiting the proliferation of rat pulmonary arterial smooth muscle cells. This study aimed to investigate the effect of echinacoside on HPH. Sprague Dawley rats were housed in a hypobaric hypoxia chamber (4500 m) for 28 days to obtain the HPH model. Echinacoside (3.75, 7.5, 15, 30 and 40 mg/kg) was administered by intraperitoneal injection from the 1st to the 28th day. The mean pulmonary artery pressure (mPAP), right ventricular hypertrophy index, hemoglobin, hematocrit, red blood cell concentration and morphological change of pulmonary arteries were evaluated. Vascular perfusion assay was used to assess the pulmonary artery function. Echinacoside reduced mPAP, hemoglobin, hematocrit, right ventricular hypertrophy index and mean wall thickness% of pulmonary arteries in HPH rats. It significantly increased maximum vasoconstriction percentage of pulmonary arteries induced by noradrenaline in a dose-dependent manner. In addition, it improved the responsiveness of pulmonary arteries to acetylcholine and sodium nitroprusside. Therefore, Echinacoside might be an effective treatment against HPH, since it regulated pulmonary artery endothelium and smooth muscle layer function and improved the remodeling of pulmonary artery.

Keywords: Echinacoside; Endothelium; Hypoxic pulmonary hypertension; Pulmonary artery function; Smooth muscle layer.

MeSH terms

  • Animals
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Glycosides / administration & dosage*
  • Glycosides / pharmacology*
  • Glycosides / therapeutic use
  • Hypertension, Pulmonary / drug therapy*
  • Hypertension, Pulmonary / etiology*
  • Hypertension, Pulmonary / physiopathology
  • Hypertension, Pulmonary / prevention & control
  • Hypoxia / complications*
  • In Vitro Techniques
  • Injections, Intraperitoneal
  • Male
  • Phytotherapy*
  • Pulmonary Artery / drug effects*
  • Pulmonary Artery / physiopathology*
  • Rats, Sprague-Dawley
  • Vascular Remodeling / drug effects*
  • Vasoconstriction / drug effects*
  • Vasodilator Agents

Substances

  • Glycosides
  • Vasodilator Agents
  • echinacoside