Fig. 1

Arterial remodeling in PPHN. The perfusion in the pulmonary circuit depends on the cardiac effort (systole). Normally, one cardiac beat causes 10% stretch. In PPHN, one cardiac beat causes less than 10% stretch. The cytoskeleton reacts to stretch. With a small strain (±5% from the artery resting length), there is heterogeneous response. With higher strain (±10% from the resting length), a huge response occurs, such as a ripping damage to the cytoskeleton. High strain is associated with cell death due to the loss of adherence to the membrane. The arterioles change their diameter in response to local conditions such as sympathetic or endocrine stimulation. Capillary walls permit exchange of oxygen and metabolites between blood and the surrounding interstitial fluids. Normally, diffusion distance is short and exchange is quick because the wall is thin. A high filamentous to globular actin (F:G) ratio increases stiffness, resulting in a thicker vessel diameter, higher pressure in remodeled versus non-remodeled vessels. Pulsation is non-harmonized due to the loss of distensibility. Remodeling is associated with hypertension, higher ROS, and lower antioxidant enzyme levels (Catalase, SOD 1,2,3, Glutatione peroxidase, NADPAH oxidases (NOX))