Korean Journal of Pediatrics 2004;47(7):707-715.
Published online July 15, 2004.
Pathophysiology of Persistent Pulmonary Hypertension of the Newborn
Yong Hoon Jun
Department of Pediatrics, College of Medicine, Inha University, Incheon, Korea
신생아 지속성 폐고혈압의 병태생리
인하대학교 의과대학 소아과학교실
Yong Hoon Jun, Email: neojun@inha.ac.kr
Persistent pulmonary hypertension of the newborn(PPHN) is a disorder characterized by persistence of the pattern of fetal circulation after birth due to a sustained elevation of pulmonary vascular resistance. The two primary events in the pathophysiology of neonatal pulmonary hypertension are hypoxic pulmonary vasoconstriction(HPV) and hypoxic pulmonary vascular remodeling(HPR). Chronic hypoxemia may cause increased muscularity of the pulmonary arteries and extension of the muscularity to more distal arteries. The mechanisms underlying neonatal hypoxic pulmonary vascular remodeling are complex and multifactorial, requiring the involvement of endothelial, vascular smooth muscle, and adventitial cells. Endothelin-1(ET-1) has strong vasoactive properties, and acts via two different receptors, ETA and ETB. In pulmonary artery, ETA receptors mediate vasoconstriction and are found on vascular smooth muscle cells, while ETB receptors that are mostly located on endothelial cells mediate vasodilation by NO and prostacyclin release. eNOS derived NO is an important mediator of pulmonary vascular response to chronic hypoxia. Atrial natriuretic peptides(ANP) plays an important role in the regulation of pulmonary arterial pressure. Vascular endothelial growth factor (VEGF) release is increased in hypoxic pulmonary arterial smooth muscle cells, and hence may be involved in hypoxic pulmonary artery remodeling and edema. Retinol is essential for fetal lung morphogenesis and subsequent normal neonatal lung growth and maturation. ATP-sensitive potassium channels may be involved in the later stage of hypoxia. Activation of these channels may counteract the vasoconstrictive effect of hypoxia.
Key Words: Persistent pulmonary hypertension of the newborn(PPHN), Hypoxic pulmonary vasoconstriction, Hypoxic pulmonary vascular remodeling, Endothelin-1(ET-1), NO, Atrial natriuretic peptide(ANP), Vascular endothelial growth factor(VEGF), Retinol, ATP-sens

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