Contribution of oxidative stress to pulmonary arterial hypertension

• DOI: 10.4330/wjc.v2.i10.316
• Publication Date: 2010-10-27T00:48:04Z
• Authors: Vincent G DeMarco
• Keywords: Hypoxia; Endothelial Dysfunction

Recent data implicate oxidative stress as a mediator of pulmonary hypertension (PH) and the associated pathological changes to vasculature right ventricle (RV).Increases in reactive oxygen species (ROS), altered redox state, elevated oxidant have been demonstrated lungs RV several animal models PH, including chronic hypoxia, monocrotaline toxicity, caveolin-1 knock-out mouse, transgenic Ren2 rat which overexpresses mouse renin gene.Generation ROS these is derived mostly from activities nicotinamide adenine dinucleotide phosphate oxidases, xanthine oxi-dase, uncoupled endothelial nitric oxide synthase.As disease progresses circulating monocytes bone marrow-derived monocytic progenitor cells are attracted accumulate vasculature.Once established, inflammatory generate secrete mitogenic fibrogenic cytokines that induce cell proliferation fibrosis vascular wall resulting progressive remodeling.Deficiencies antioxidant enzymes also contribute hypertensive states.Current therapies were developed improve function, reduce artery pressure, slow progression remodeling by targeting deficiencies either NO (PDE-type 5 inhibition) or PGI2 (prostacyclin analogs), excessive synthesis ET-1 (ET receptor blockers) with intent patient clinical status survival.New may some extent, but long term management has not achieved mortality still high.Although little known concerning effects current arterial treatments on structure interest this area increasing.Development therapeutic strategies simultaneously target pathology be beneficial reducing failure.