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Mechanism of pulmonary vasculature remodeling and basis of therapeutic intervention in PPHN From animal studies there is good evidence that remodeling of the pulmonary vasculature occurs as a result of the disruption of the following one or more pathways: 1) nitric oxide-cGMP pathway, 2) prostacyclin-cAMP pathway, 3) endothelin signaling pathway and 4) oxidant stress pathway (5, 6)