Developmental expression of vasoactive and growth factors in human lung. Role in pulmonary vascular resistance adaptation at birth.
The factors that mediate the postnatal fall in pulmonary vascular resistance, which is crucial for normal gas exchange, are not fully understood. The endothelium has been implicated in this phenomenon, through the release of vasorelaxant factors such as nitric oxide (NO). Human pulmonary expression of endothelial NO synthase increases up to 31 wk of gestation, together with vascular endothelial growth factor (VEGF), and both factors potently mediate pulmonary angiogenesis and vasorelaxation. During the perinatal period, when pulmonary vasodilatation is maximal, endothelial NO synthase and VEGF are weakly expressed. This raises the involvement of vasorelaxant factors other than NO at birth. One candidate is endothelial-derived hyperpolarizing factor, which induces smooth muscle cell hyperpolarization by activating K(ATP) channels. The marked vasorelaxation induced by activation of these channels in newborn animals, and their strong perinatal expression in the human lung, suggest their involvement during this phase. Another candidate is endothelin (ET)-1, together with its receptors ET-A and ET-B. ET-A receptors are located exclusively on smooth muscle cells and mediate vasoconstriction, whereas ET-B receptors mediate vasoconstriction when located on smooth muscle cells and vasodilatation when located on endothelial cells. ET-B receptors, which are strongly expressed in the human fetal lung both at the end of gestation and after birth, may be involved in perinatal pulmonary vasodilatation. Thus, in human fetal lung, K(ATP) channels and ET-B receptors could be important in mediating the perinatal pulmonary vasodilatation crucial for adapting the pulmonary circulation to extrauterine life.
Lévy
Marilyne
M
UPRES EA220, Laboratoired'Immunologie Pulmonaire, Faculté de Médecine, Paris V, France. marilyne.levy@nck.ap-hop-paris.fr
Maurey
Christelle
C
Dinh-Xuan
A Tuan
AT
Vouhé
Pascal
P
Israël-Biet
Dominique
D
D000064:Acclimatization; D000255:Adenosine Triphosphate / Q000737:chemistry; D000818:Animals; D000831:Animals, Newborn; D018507:Gene Expression Regulation, Developmental; D006133:Growth Substances / Q000378:metabolism*; D006801:Humans; D007231:Infant, Newborn; D008168:Lung / Q000196:embryology / Q000378:metabolism*; D008954:Models, Biological; D032389:Myocytes, Smooth Muscle / Q000166:cytology; D009569:Nitric Oxide / Q000378:metabolism; D011652:Pulmonary Circulation; D044022:Receptor, Endothelin A / Q000378:metabolism; D044023:Receptor, Endothelin B / Q000378:metabolism; D013997:Time Factors; D014655:Vascular Resistance; D014665:Vasodilator Agents / Q000494:pharmacology
D006133:Growth Substances; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D014665:Vasodilator Agents; D009569:Nitric Oxide; D000255:Adenosine Triphosphate