Roles of the Angiotensin System in Neonatal Lung Injury and Disease.

The renin-angiotensin system (RAS) has long been known as a regulator of blood pressure and fluid homeostasis. In past several decades, local renin-angiotensin systems have been discovered in various tissues and novel actions of angiotensin II (ANGII) have emerged as an immunomodulator and profibrotic molecule. The enzyme responsible for its synthesis, angiotensin-converting-enzyme (ACE), is present in high concentrations in lung tissue. ACE cleaves angiotensin I (ANG I) to generate angiotensin II (ANGII), whereas ACE2 inactivates ANGII and is a negative regulator of the system. The RAS has been implicated in the pathogenesis of pulmonary hypertension, acute lung injury and experimental lung fibrosis. Recent studies in animal and humans indicate that the RAS also plays a critical role in fetal and neonatal lung diseases. Further investigations are needed to better understand the role of RAS, ACE and ACE-2 in neonatal lung injury. With more clarity and understanding, the RAS and/or ACE-2 may ultimately prove to constitute potential therapeutic targets for the treatment of neonatal lung diseases. This manuscript reviews the evidence supporting a role for RAS in neonatal lung injury and discusses new possibilities for therapeutic approaches.