Fig. 2.

Alterations in biochemical pathways in pulmonary vascular endothelial and smooth muscle cells in normal and persistent pulmonary hypertension of the newborn (PPHN). Endothelial dysfunction, smooth muscle hyperplasia and hypertrophy and adventitial thickening are common in PPHN. Increased oxidative stress with high levels of superoxide anions (${\text{O}}_2^{•-}$) alters several enzymes in the nitric oxide (NO) pathway increasing the risk of vasoconstriction. ADMA - asymmetric dimethyl arginine; eNOS – endothelial nitric oxide synthase; ET – endothelin; SOD – superoxide dismutase; MnSOD – Manganese, mitochondrial superoxide dismutase; EC-SOD – extracellular superoxide dismutase; sGC – soluble guanylate cyclase; PDE 5 – phosphodiesterase 5; GTP – guanosine triphosphate; cGMP – cyclic guanosine monophosphate; NO – nitric oxide; CaM – calmodulin; Modified from Polin and Fox Fetal and Neonatal Physiology, 6th edition, copyright Satyan Lakshminrusimha (with permission).