Document Detail


Moderate postnatal hyperoxia accelerates lung growth and attenuates pulmonary hypertension in infant rats after exposure to intra-amniotic endotoxin.
MedLine Citation:
PMID:  20709730     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
To determine the separate and interactive effects of fetal inflammation and neonatal hyperoxia on the developing lung, we hypothesized that: 1) antenatal endotoxin (ETX) causes sustained abnormalities of infant lung structure; and 2) postnatal hyperoxia augments the adverse effects of antenatal ETX on infant lung growth. Escherichia coli ETX or saline (SA) was injected into amniotic sacs in pregnant Sprague-Dawley rats at 20 days of gestation. Pups were delivered 2 days later and raised in room air (RA) or moderate hyperoxia (O₂, 80% O₂ at Denver's altitude, ∼65% O₂ at sea level) from birth through 14 days of age. Heart and lung tissues were harvested for measurements. Intra-amniotic ETX caused right ventricular hypertrophy (RVH) and decreased lung vascular endothelial growth factor (VEGF) and VEGF receptor-2 (VEGFR-2) protein contents at birth. In ETX-exposed rats (ETX-RA), alveolarization and vessel density were decreased, pulmonary vascular wall thickness percentage was increased, and RVH was persistent throughout the study period compared with controls (SA-RA). After antenatal ETX, moderate hyperoxia increased lung VEGF and VEGFR-2 protein contents in ETX-O₂ rats and improved their alveolar and vascular structure and RVH compared with ETX-RA rats. In contrast, severe hyperoxia (≥95% O₂ at Denver's altitude) further reduced lung vessel density after intra-amniotic ETX exposure. We conclude that intra-amniotic ETX induces fetal pulmonary hypertension and causes persistent abnormalities of lung structure with sustained pulmonary hypertension in infant rats. Moreover, moderate postnatal hyperoxia after antenatal ETX restores lung growth and prevents pulmonary hypertension during infancy.
Authors:
Jen-Ruey Tang; Gregory J Seedorf; Vincent Muehlethaler; Deandra L Walker; Neil E Markham; Vivek Balasubramaniam; Steven H Abman
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2010-08-13
Journal Detail:
Title:  American journal of physiology. Lung cellular and molecular physiology     Volume:  299     ISSN:  1522-1504     ISO Abbreviation:  Am. J. Physiol. Lung Cell Mol. Physiol.     Publication Date:  2010 Dec 
Date Detail:
Created Date:  2010-12-06     Completed Date:  2011-01-13     Revised Date:  2013-05-29    
Medline Journal Info:
Nlm Unique ID:  100901229     Medline TA:  Am J Physiol Lung Cell Mol Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  L735-48     Citation Subset:  IM    
Affiliation:
Dept. of Pediatrics, Univ. of Colorado Health Sciences Center, Aurora, CO 80045, USA. Jen-Ruey.Tang@ucdenver.edu
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MeSH Terms
Descriptor/Qualifier:
Animals
Animals, Newborn*
Endotoxins / pharmacology*
Female
Fetus / anatomy & histology,  drug effects*
Gestational Age
Humans
Hyperoxia*
Hypertension, Pulmonary / chemically induced*,  physiopathology
Hypertrophy, Right Ventricular / chemically induced
Infant
Lung / anatomy & histology,  drug effects*,  growth & development*,  physiopathology
Oxygen / metabolism
Pregnancy
Prenatal Exposure Delayed Effects
Rats
Rats, Sprague-Dawley
Grant Support
ID/Acronym/Agency:
R01-HL-68702/HL/NHLBI NIH HHS; T32-HL-07670/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Endotoxins; 7782-44-7/Oxygen
Comments/Corrections

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