title: Perinatal nitric oxide therapy prevents adverse effects of perinatal hypoxia on the adult pulmonary circulation.
abstract: Adverse events in utero are associated with the occurrence of chronic diseases in adulthood. We previously demonstrated in mice that perinatal hypoxia resulted in altered pulmonary circulation in adulthood, with a decreased endothelium-dependent relaxation of pulmonary arteries, associated with long-term alterations in the nitric oxide (NO)/cyclic GMP pathway. The present study investigated whether inhaled NO (iNO) administered simultaneously to perinatal hypoxia could have potential beneficial effects on the adult pulmonary circulation. Indeed, iNO is the therapy of choice in humans presenting neonatal pulmonary hypertension. Long-term effects of neonatal iNO therapy on adult pulmonary circulation have not yet been investigated. Pregnant mice were placed in hypoxia (13% O2) with simultaneous administration of iNO 5 days before delivery until 5 days after birth. Pups were then raised in normoxia until adulthood. Perinatal iNO administration completely restored acetylcholine-induced relaxation, as well as endothelial nitric oxide synthase protein content, in isolated pulmonary arteries of adult mice born in hypoxia. Right ventricular hypertrophy observed in old mice born in hypoxia compared to controls was also prevented by perinatal iNO treatment. Therefore, simultaneous administration of iNO during perinatal hypoxic exposure seems able to prevent adverse effects of perinatal hypoxia on the adult pulmonary circulation.
authors.affiliation: Neonatal Research Laboratory, Clinic of Neonatology, Department of Pediatrics, Lausanne University Hospital, 1011 Lausanne, Switzerland.
authors.forename: Anne-Christine
authors.initials: AC
authors.lastname: Peyter
authors.affiliation: Neonatal Research Laboratory, Clinic of Neonatology, Department of Pediatrics, Lausanne University Hospital, 1011 Lausanne, Switzerland.
authors.forename: Flavien
authors.initials: F
authors.lastname: Delhaes
authors.affiliation: Neonatal Research Laboratory, Clinic of Neonatology, Department of Pediatrics, Lausanne University Hospital, 1011 Lausanne, Switzerland.
authors.forename: Giacomo
authors.initials: G
authors.lastname: Diaceri
authors.affiliation: Neonatal Research Laboratory, Clinic of Neonatology, Department of Pediatrics, Lausanne University Hospital, 1011 Lausanne, Switzerland.
authors.forename: Steeve
authors.initials: S
authors.lastname: Menétrey
authors.affiliation: Neonatal Research Laboratory, Clinic of Neonatology, Department of Pediatrics, Lausanne University Hospital, 1011 Lausanne, Switzerland.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Tolsa
mesh_terms: D000280:Administration, Inhalation; D000328:Adult; D000818:Animals; D006152:Cyclic GMP / Q000378:metabolism; D005260:Female; D006801:Humans; D017380:Hypertrophy, Right Ventricular / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D000860:Hypoxia / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D009569:Nitric Oxide / Q000008:administration & dosage* / Q000378:metabolism; D010100:Oxygen / Q000008:administration & dosage / Q000009:adverse effects; D011247:Pregnancy; D011652:Pulmonary Circulation; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D009569:Nitric Oxide; D006152:Cyclic GMP; D010100:Oxygen
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