| Cyclooxygenase-2 inhibitors constrict the fetal lamb ductus arteriosus both in vitro and in vivo. | |
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MedLine Citation:
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PMID: 10848516 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Nonselective cyclooxygenase (COX) inhibitors are potent tocolytic agents; however, they also have adverse fetal effects such as constriction of the fetal ductus arteriosus. Recently, selective COX-2 inhibitors have been used in the management of preterm labor in the hope of avoiding fetal complications. However, both COX-1 and -2 are expressed by cells of the ductus arteriosus. We used fetal lambs (0.88 gestation) to assess the ability of selective COX-2 inhibitors celecoxib and NS398 to affect the ductus arteriosus. Both selective COX-2 inhibitors decreased PGE(2) and 6ketoPGF(1alpha) production in vitro; both inhibitors constricted the isolated ductus in vitro. The nonselective COX-1/COX-2 inhibitor indomethacin produced a further reduction in PG release and an additional increase in ductus tension in vitro. We used a prodrug of celecoxib to achieve 1.4 +/- 0.6 microg/ml, mean +/- standard deviation, of the active drug in vivo. This concentration of celecoxib produced both an increase in pressure gradient and resistance across the ductus; celecoxib also decreased fetal plasma concentrations of PGE(2) and 6ketoPGF(1alpha). Indomethacin (0.7 +/- 0.2 microg/ml) produced a significantly greater fall in ductus blood flow than celecoxib and tended to have a greater effect on ductus resistence in vivo. We conclude that caution should be used when recommending COX-2 inhibitors for use in pregnant women, because COX-2 appears to play a significant role in maintaining patency of the fetal ductus arteriosus. |
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Authors:
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Y Takahashi; C Roman; S Chemtob; M M Tse; E Lin; M A Heymann; R I Clyman |
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Publication Detail:
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Type: In Vitro; Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: American journal of physiology. Regulatory, integrative and comparative physiology Volume: 278 ISSN: 0363-6119 ISO Abbreviation: Am. J. Physiol. Regul. Integr. Comp. Physiol. Publication Date: 2000 Jun |
Date Detail:
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Created Date: 2000-07-06 Completed Date: 2000-07-06 Revised Date: 2007-11-15 |
Medline Journal Info:
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Nlm Unique ID: 100901230 Medline TA: Am J Physiol Regul Integr Comp Physiol Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: R1496-505 Citation Subset: IM |
Affiliation:
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Cardiovascular Research Institute, University of California, San Francisco, San Francisco, California 94143-0544, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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6-Ketoprostaglandin F1 alpha
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blood Animals Cyclooxygenase 1 Cyclooxygenase 2 Cyclooxygenase 2 Inhibitors Cyclooxygenase Inhibitors / blood, pharmacology Dinoprostone / blood Ductus Arteriosus / drug effects*, enzymology* Epoprostenol / metabolism Female Hemodynamics / drug effects, physiology Indomethacin / blood, pharmacology Isoenzymes / antagonists & inhibitors*, metabolism, pharmacology Nitrobenzenes / pharmacology Nitroprusside / pharmacology Oxygen / pharmacology Pregnancy Prostaglandin-Endoperoxide Synthases / metabolism, pharmacology Pulmonary Artery / drug effects, physiology Pyrazoles Sheep Sulfonamides / blood, pharmacology Vasoconstriction / drug effects* Vasodilator Agents / pharmacology |
| Grant Support | |
ID/Acronym/Agency:
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HD32518/HD/NICHD NIH HHS; HL46691/HL/NHLBI NIH HHS; HL56061/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Cyclooxygenase 2 Inhibitors; 0/Cyclooxygenase Inhibitors; 0/Isoenzymes; 0/Nitrobenzenes; 0/Pyrazoles; 0/Sulfonamides; 0/Vasodilator Agents; 123653-11-2/N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; 15078-28-1/Nitroprusside; 169590-42-5/celecoxib; 35121-78-9/Epoprostenol; 363-24-6/Dinoprostone; 53-86-1/Indomethacin; 58962-34-8/6-Ketoprostaglandin F1 alpha; 7782-44-7/Oxygen; EC 1.14.99.1/Cyclooxygenase 1; EC 1.14.99.1/Cyclooxygenase 2; EC 1.14.99.1/Prostaglandin-Endoperoxide Synthases |
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