Cannabidiol Attenuates Pulmonary Arterial Hypertension by Normalizing the Mitochondrial Function in Vascular Smooth Muscle Cells

Abstract

Pulmonary artery hypertension (PAH) is a chronic disease associated with enhanced proliferation of pulmonary artery smooth muscle cells (PASMCs) and dysfunctional mitochondria, which was with limited therapeutic options. It has been proved that cannabidiol (CBD) had antioxidant effects in many cardiovascular diseases, whereas the efficacy of CBD in PAH is unknown. To defined the effect of CBD in PAH, we explored the functions of CBD in both PASMCs proliferation test in vitro, and preventive and therapeutic PAH rodent models in vivo. The roles of CBD in mitochondria function and the oxidant stress were assessed in human PASMCs and PAH mice. We found that CBD significantly inhibited hyperproliferation of hypoxia-induced PASMCs, and intragastrically administered CBD could reverse the pathological changes in both Sugen-hypoxia and MCT- induced PAH mice models. Mechanical analysis demonstrated that CBD alleviated PAH by recovering mitochondrial energy metabolism, normalizing the hypoxia-induced oxidant stress, inhibiting abnormal glycolysis and lactate accumulation in cannabinoids receptors-independent manner. Thus, CBD could be a potential drug for PAH.

Experimental Studies and First Retrospective Clinical Data Suggest a Possible Benefit of CBD in COVID-19

“…A particularly vulnerable group are patients with pulmonary arterial hypertension. Although uncommon with COVID-19, it is worth to mention that CBD (10 mg/kg/day) was able to reduce monocrotalineinduced pulmonary arterial hypertension in two animal models [29,30]. As lung injury in COVID-19 may be increased by hypoxic ischemic brain damage, brain-protective properties of CBD are of further importance.…”