Transition from placental to air breathing stimulates haem-oxygenase-1 expression without functional consequence for pulmonary vascular adaptation in pigs and mice.
1. In systemic vessels, haem-oxygenase (HO) is induced during oxidative stress and known to modulate vasodilatation and vascular remodelling. At birth, with the transition from placental to air breathing, the pulmonary vessels are exposed to oxidative stress and undergo well-documented remodelling processes. Thus, we investigated the role of HO in the lung during adaptation to extra-uterine life using a pig and mouse model. In addition to the novel data presented with regard to one isoform, HO-1, this study is among the first to describe the pulmonary vascular remodelling in the mouse after birth. 2. We show, for the first time, that another isoform, HO-2, is present constitutively at birth and HO-1 protein is induced in the porcine and murine lung after birth in vascular and airway structures, peaking at 14 days in the pig and at about 4 days in the mouse. Furthermore, we show that HO-1 mRNA declines after birth in the mouse lung. 3. Inhibitors of HO did not modify vasodilator responses in vessels from 14-day-old pigs. 4. Moreover, lungs from HO-1-deficient mice developed normally after birth. 5. HO-1 is induced at birth but plays no role in the development of vasodilator responses or remodelling that occurs at this time. These data suggest that HO-1 expression at birth is a redundant response to oxidative stress in the lungs of healthy mammals. However, it remains possible that this pathway protects if complications occur during or after birth.
Stanford
Salome J
SJ
Cardiothoracic Pharmacology, UCCM, The Royal Brompton & Harefield N.H.S. Trust, Imperial College, National Heart and Lung Institute, Dovehouse Street, Sydney Street, London, UK.
Hislop
Alison A
AA
Oltmanns
Ute
U
Nabel
Elizabeth G
EG
Sang
Hong
H
Haworth
Shelia G
SG
Mitchell
Jane A
JA
D000222:Adaptation, Physiological / Q000502:physiology*; D000818:Animals; D000831:Animals, Newborn; D015153:Blotting, Western; D006419:Heme Oxygenase (Decyclizing) / Q000096:biosynthesis* / Q000235:genetics; D051547:Heme Oxygenase-1; D008168:Lung / Q000098:blood supply / Q000201:enzymology / Q000254:growth & development / Q000502:physiology*; D008565:Membrane Proteins; D051379:Mice; D018345:Mice, Knockout; D009119:Muscle Contraction / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000254:growth & development / Q000502:physiology; D011651:Pulmonary Artery / Q000254:growth & development / Q000502:physiology*; D012143:Respiratory Physiological Phenomena; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013552:Swine
D008565:Membrane Proteins; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1; C496542:Hmox1 protein, mouse