| Hydrocortisone normalizes oxygenation and cGMP regulation in lambs with persistent pulmonary hypertension of the newborn. | |
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MedLine Citation:
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PMID: 22198909 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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In the pulmonary vasculature, cGMP levels are regulated by soluble guanylate cyclase (sGC) and phosphodiesterase 5 (PDE5). We previously reported that lambs with persistent pulmonary hypertension of the newborn (PPHN) demonstrate increased reactive oxygen species (ROS) and altered sGC and PDE5 activity, with resultant decreased cGMP. The objective of this study was to evaluate the effects of hydrocortisone on pulmonary vascular function, ROS, and cGMP in the ovine ductal ligation model of PPHN. PPHN lambs were ventilated with 100% O(2) for 24 h. Six lambs received 5 mg/kg hydrocortisone every 8 h times three doses (PPHN-hiHC), five lambs received 3 mg/kg hydrocortisone followed by 1 mg·kg(-1)·dose(-1) times two doses (PPHN-loHC), and six lambs were ventilated with O(2) alone (PPHN). All groups were compared with healthy 1-day spontaneously breathing lambs (1DSB). O(2) ventilation of PPHN lambs decreased sGC activity, increased PDE5 activity, and increased ROS vs. 1DSB lambs. Both hydrocortisone doses significantly improved arterial-to-alveolar ratios relative to PPHN lambs, decreased PDE5 activity, and increased cGMP relative to PPHN lambs. High-dose hydrocortisone also increased sGC activity, decreased PDE5 expression, decreased ROS, and increased total vascular SOD activity vs. PPHN lambs. These data suggest that hydrocortisone treatment in clinically relevant doses improves oxygenation and decreases hyperoxia-induced changes in sGC and PDE5 activity, increasing cGMP levels. Hydrocortisone reduces ROS levels in part by increasing SOD activity in PPHN lambs ventilated with 100% O(2.) We speculate that hydrocortisone increases cGMP by direct effects on sGC and PDE5 expression and by attenuating abnormalities induced by oxidant stress. |
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Authors:
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Marta Perez; Satyan Lakshminrusimha; Stephen Wedgwood; Lyubov Czech; Sylvia F Gugino; James A Russell; Kathryn N Farrow; Robin H Steinhorn |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2011-12-23 |
Journal Detail:
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Title: American journal of physiology. Lung cellular and molecular physiology Volume: 302 ISSN: 1522-1504 ISO Abbreviation: Am. J. Physiol. Lung Cell Mol. Physiol. Publication Date: 2012 Mar |
Date Detail:
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Created Date: 2012-03-16 Completed Date: 2012-07-16 Revised Date: 2013-05-22 |
Medline Journal Info:
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Nlm Unique ID: 100901229 Medline TA: Am J Physiol Lung Cell Mol Physiol Country: United States |
Other Details:
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Languages: eng Pagination: L595-603 Citation Subset: IM |
Affiliation:
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Northwestern University, Chicago, Illinois, USA. mtperez@childrensmemorial.org |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Animals, Newborn Cyclic GMP / metabolism* Cyclic Nucleotide Phosphodiesterases, Type 5 / genetics, metabolism Guanylate Cyclase / metabolism Humans Hydrocortisone / pharmacology* Hyperoxia / drug therapy, genetics, metabolism, physiopathology Infant, Newborn Oxidative Stress / drug effects, genetics Oxygen / metabolism* Persistent Fetal Circulation Syndrome / drug therapy*, genetics, metabolism*, physiopathology Pulmonary Artery / drug effects*, metabolism, physiopathology Reactive Oxygen Species / metabolism Receptors, Cytoplasmic and Nuclear / metabolism Sheep Superoxide Dismutase / metabolism |
| Grant Support | |
ID/Acronym/Agency:
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HL-086715/HL/NHLBI NIH HHS; HL-54705/HL/NHLBI NIH HHS; K08 HL086715/HL/NHLBI NIH HHS; R01 HL054705/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Reactive Oxygen Species; 0/Receptors, Cytoplasmic and Nuclear; 50-23-7/Hydrocortisone; 7665-99-8/Cyclic GMP; 7782-44-7/Oxygen; EC 1.15.1.1/Superoxide Dismutase; EC 3.1.4.35/Cyclic Nucleotide Phosphodiesterases, Type 5; EC 4.6.1.2/Guanylate Cyclase; EC 4.6.1.2/soluble guanylyl cyclase |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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