Document Detail

Chronic intrauterine pulmonary hypertension impairs endothelial nitric oxide synthase in the ovine fetus.
MedLine Citation:
PMID:  9176268     Owner:  NLM     Status:  MEDLINE    
Endothelial (e) nitric oxide synthase (NOS) activity modulates pulmonary vascular tone in the normal fetus and decreases pulmonary vascular resistance (PVR) at birth. Mechanisms contributing to sustained elevations of PVR and the failure of postnatal adaptation at birth are uncertain but may include decreased eNOS activity. To test this hypothesis, we studied the effects of chronic intrauterine pulmonary hypertension on lung eNOS content and NOS activity in an ovine model of perinatal pulmonary hypertension and in normal lambs. We measured eNOS mRNA and protein content by Northern and Western blot analyses, respectively. Calcium-dependent and total NOS activities were determined by assaying the conversion of L-[14C]arginine to L-[14C]citrulline from lung homogenates. To determine the effects of intrauterine hypertension on lung eNOS content, fetal lung tissue was harvested 8-12 days after intrauterine closure of the ductus arteriosus (DA) performed at 125-128 days of gestation (term = 147 days). Although positive immunostaining for eNOS persisted in lung vascular endothelium, eNOS protein content was reduced by 48%, as measured by Western analysis (P < 0.001). Chronic hypertension reduced lung eNOS mRNA content by 30% (P < 0.05). Compared with age-matched controls, Ca(2+)-dependent NOS activity was decreased after DA ligation by 75% (P < 0.01). We conclude that chronic intrauterine pulmonary hypertension decreases eNOS in the fetal lung. We speculate that decreased NO production contributes to failure of postnatal adaptation in this experimental model of persistent pulmonary hypertension of the newborn.
E Villamor; T D Le Cras; M P Horan; A C Halbower; R M Tuder; S H Abman
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  The American journal of physiology     Volume:  272     ISSN:  0002-9513     ISO Abbreviation:  Am. J. Physiol.     Publication Date:  1997 May 
Date Detail:
Created Date:  1997-07-08     Completed Date:  1997-07-08     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0370511     Medline TA:  Am J Physiol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  L1013-20     Citation Subset:  IM    
Pediatric Heart-Lung Center, University of Colorado School of Medicine, Denver 80218, USA.
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MeSH Terms
Blotting, Northern
Chronic Disease
Endothelium, Vascular / embryology*,  enzymology
Fetal Diseases / enzymology*
Fetus / enzymology*
Hypertension, Pulmonary / enzymology*
Infant, Newborn
Nitric Oxide Synthase / genetics,  metabolism*
Persistent Fetal Circulation Syndrome / enzymology
RNA, Messenger / metabolism
Sheep / embryology
Grant Support
Reg. No./Substance:
0/RNA, Messenger; EC Oxide Synthase

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