Pressure vs Flow-Induced Pulmonary Hypertension

The pathophysiology of pulmonary hypertension (PH) is multifactorial, complex, and incompletely understood. However, it is known that abnormal mechanical forces within the pulmonary vasculature participate in the disease process. The pulmonary vasculature is continually exposed to hemodynamic forces that include: (1) shear stress, the tangential friction force acting on the vessel wall due to blood flow; (2) hydrostatic pressure, the perpendicular force acting on the vascular wall; and (3) cyclic strain, the circumferential stretch of the vessel wall. Mechanosensors on pulmonary vascular endothelial cells detect these forces and transduce them into biochemical signals that trigger vascular responses (Figure 1). Among the various force-induced signaling molecules, nitric oxide (NO), reactive oxygen species (ROS), and endothelin-1 (ET-1) have been implicated in vascular health and disease. For example, increases in physiologic shear stress associated with increased cardiac output (ie, during exercise) result in induction of NO production with decreased ROS and ET-1, facilitating pulmonary vasodilation and increased flow. However, the pathologic pulmonary vasculature may induce supraphysiologic levels of shear stress, pressure, and cyclic strain resulting in decreased NO with increased ROS and ET-1. Thus, abnormal hemodynamic forces develop in and participate in the disease progression of most forms of pulmonary vascular disease (PVD). However, the influence of hemodynamic forces in the pathobiology of PVD is most clearly demonstrated in patients with PH secondary to congenital heart disease (CHD).