FIGURE 12.

Tissue inflammation and reactive species are important to long-term hypoxia induced pulmonary hypertension. Hypoxic stress leads to the production of reactive species including O₂⁻, OH, H₂O₂, as well as ONOO⁻. These species are generated in many cell types associated with the pulmonary vasculature ranging from endothelial and smooth muscle cells to macrophages and other immune cells important to tissue inflammation. The reactive species then influence mRNA transcription, protein translation, and posttranslational processes. The combination of tissue inflammation and reactive species production leads to pulmonary hypertension though structural alterations that result in vascular remodeling, as well as regulatory and functional changes that lead to enhanced vasoconstriction, and depressed in vasodilatory capacity.