Cannabidiol attenuates pulmonary arterial hypertension by improving vascular smooth muscle cells mitochondrial function

Theranostics. 2021 Mar 11;11(11):5267-5278. doi: 10.7150/thno.55571. eCollection 2021.


Rationale: Pulmonary arterial hypertension (PAH) is a chronic disease associated with enhanced proliferation of pulmonary artery smooth muscle cells (PASMCs) and dysfunctional mitochondria, and the clinical therapeutic option for PAH is very limited. Recent studies showed that cannabidiol (CBD), a non-psychoactive constituent of cannabinoids, possessed antioxidant effect towards several cardiovascular diseases, whereas the mechanistic effect of CBD in PAH is unknown. Methods: In this study, the effects of CBD in PAH were determined by analyzing its preventive and therapeutic actions in PAH rodent models in vivo and PASMCs' proliferation test in vitro. Additionally, CBD's roles in mitochondrial function and oxidant stress were also assessed in PASMCs. Results: We found that CBD reversed the pathological changes observed in both Sugen-hypoxia and monocrotaline-induced PAH rodent models in a cannabinoid receptors-independent manner. Our results also demonstrated that CBD significantly inhibited the PASMCs' proliferation in PAH mice with less inflammation and reactive oxygen species levels. Moreover, CBD alleviated rodent PAH by recovering mitochondrial energy metabolism, normalizing the hypoxia-induced oxidant stress, reducing the lactate overaccumulation and abnormal glycolysis. Conclusions: Taken together, these findings confirm an important role for CBD in PAH pathobiology.

Keywords: Antioxidant; Cannabinoids; Glycolysis.; Mitochondria networks; Pulmonary arterial hypertension.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cannabidiol / pharmacology*
  • Cell Proliferation / drug effects
  • Disease Models, Animal
  • Glycolysis / drug effects
  • Hypoxia / metabolism
  • Inflammation / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mitochondria / drug effects*
  • Mitochondria / metabolism
  • Monocrotaline / pharmacology
  • Muscle, Smooth, Vascular / drug effects*
  • Muscle, Smooth, Vascular / metabolism
  • Myocytes, Smooth Muscle / drug effects*
  • Myocytes, Smooth Muscle / metabolism
  • Oxidative Stress / drug effects
  • Pulmonary Arterial Hypertension / drug therapy*
  • Pulmonary Arterial Hypertension / metabolism
  • Pulmonary Artery
  • Reactive Oxygen Species / metabolism
  • Vascular Remodeling


  • Reactive Oxygen Species
  • Cannabidiol
  • Monocrotaline