The NOX on pulmonary hypertension.

摘要

Chronic pulmonary arterial hypertension (PAH) is a devastating clinical disorder that contributes to the morbidity and mortality of adult and pediatric patients with a wide range of lung and heart diseases. Diseases leading to pulmonary hypertension are frequently associated with hypoxia within discrete areas of the lung. Acutely, the regional response to hypoxia is a reversible contraction of pulmonary artery smooth muscle cells (PASMC), which is a protective physiologic response that serves to redirect blood to better-ventilated areas of the lung. This constrictor response of PASMC contrasts with that of systemic arterial smooth muscle cells, which usually relax in response to hypoxia, indicating that oxygen (O2) sensing mechanisms in vascular smooth muscle are adapted to the environment from which they are derived. Importantly, chronic hypoxia induces irreversible changes of profound vascular remodeling characterized by medial and adventitial thickening of the muscular and elastic vessels and muscularization of previously nonmuscu-larized more distal small vessels. This is the basis for debilitating persistent PAH.