ABSTRACT
Neonatal pulmonary hypertension (PH) is a spectrum of disorders caused by in utero and postnatal insults to the developing pulmonary circulation. The clinical presentation can be sudden or insidious. The breadth of knowledge needed to understand the pathophysiology and devise therapies for the broad spectrum of neonatal PH has led to the creation of numerous experimental models in animals at different developmental stages. To create PH, investigators manipulate environmental and hemodynamic conditions known to impact pulmonary vascular tone and/or structure. To achieve meaningful translational relevance to human newborns, the ideal stimulus both elevates tone and causes pertinent structural changes in the pulmonary vasculature, mimicking the pathophysiology of human newborns with treatment-resistant PH. Endogenously produced vasoconstrictors, including thromboxane and endothelin-1, have long been acknowledged to contribute to the development of neonatal PH, in humans and in a variety of experimental animal models. This chapter will first describe the various injurious stimuli, developmental stages, and animal species that are used to create neonatal models of PH. Then, the contribution of endogenously produced vasoconstrictors to the development of PH in neonatal animal models will be discussed.
