Role of reactive oxygen species in vascular remodeling associated with pulmonary hypertension.
Several manifestations of neonatal pulmonary hypertension are associated with vascular remodeling, resulting in increased muscularity of the small pulmonary arteries. Abnormal structural development of the pulmonary vasculature has been implicated in persistent pulmonary hypertension of the newborn (PPHN). Increased plasma levels of the vasoconstrictor endothelin-1 (ET-1) have been demonstrated in patients with PPHN, which is likely to contribute to hypertension. In addition, several studies have identified a role for ET-1 in the proliferation of vascular smooth muscle cells (SMCs), suggesting that ET-1 may also be involved in the vascular remodeling characteristic of this disease. However, the mechanisms of ET-1-induced SMC proliferation are unclear and appear to differ between cells from different origins within the vasculature. In SMCs isolated from fetal pulmonary arterial cells, ET-1 stimulated proliferation via an induction of reactive species (ROS). Furthermore, other lines of evidence have demonstrated the involvement of ROS in ET-1-stimulated SMC growth, suggesting that ROS may be a common factor in the mechanisms involved. This review discusses the potential roles for ROS in the abnormal pulmonary vascular development characteristic of PPHN, and the treatment strategies arising from our increasing knowledge of the molecular mechanisms involved.
Department of Pediatrics, Northwestern University, Chicago, IL 60611, USA.
Stephen
S
Wedgwood
Stephen M
SM
Black
D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D002455:Cell Division; D019332:Endothelin-1 / Q000378:metabolism; D004730:Endothelium, Vascular / Q000378:metabolism; D006801:Humans; D006976:Hypertension, Pulmonary / Q000473:pathology*; D008954:Models, Biological; D009569:Nitric Oxide / Q000378:metabolism / Q000627:therapeutic use; D020030:Nitric Oxide Donors / Q000378:metabolism; D011651:Pulmonary Artery / Q000473:pathology; D017382:Reactive Oxygen Species; D017466:Receptors, Endothelin / Q000378:metabolism; D014652:Vascular Diseases / Q000473:pathology*
D000975:Antioxidants; D019332:Endothelin-1; D020030:Nitric Oxide Donors; D017382:Reactive Oxygen Species; D017466:Receptors, Endothelin; D009569:Nitric Oxide