| Blockade of PGHS-2 inhibits the hypothalamus-pituitary-adrenal axis response to cerebral hypoperfusion in the sheep fetus. | |
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MedLine Citation:
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PMID: 19297537 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Decreases in fetal blood pressure stimulate homeostatic stress responses that help return blood pressure to normal levels. Fetal hypothalamus-pituitary-adrenal (HPA) axis responses to hypotension are mediated by chemoreceptor and baroreceptor reflexes and ischemia of the fetal central nervous system. Indomethacin, a nonselective inhibitor of prostaglandin endoperoxide synthase (PGHS)-1 and -2, attenuates the HPA response to hypotension in the fetus. The present study was designed to test the hypothesis that selective inhibition of PGHS-2 also inhibits the HPA response to cerebral hypoperfusion. We studied 13 chronically catheterized fetal sheep (126-136 days gestation). Five fetal sheep were subjected to intracerebroventricular infusion of nimesulide (0.01 mg/day), a specific inhibitor of PGHS-2, and eight were treated with vehicle (DMSO in water) for 5 days. Each fetus was subjected to a 10-min period of brachiocephalic occlusion, which decreased carotid arterial pressure approximately 75% and reflexively increased fetal plasma concentrations of ACTH, POMC, cortisol, and femoral arterial pressure, and decreased fetal heart rate. Nimesulide significantly inhibited the ACTH response to the BCO, while significantly augmenting the reflex cardiovascular response and altering fetal heart rate variability consistent with increased sympathetic nervous system activity. The results of this study demonstrate that the activity of PGHS-2 in the brain is a necessary component of the fetal HPA response to cerebral hypoperfusion in the late-gestation fetal sheep. These results are consistent with those of recent study, in which we demonstrated that the preparturient increase in fetal ACTH secretion depends upon PGHS-2 activity within the fetal brain. |
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Authors:
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Charles E Wood; Melanie Powers Fraites; Maureen Keller-Wood |
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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: 2009-03-18 |
Journal Detail:
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Title: American journal of physiology. Regulatory, integrative and comparative physiology Volume: 296 ISSN: 0363-6119 ISO Abbreviation: Am. J. Physiol. Regul. Integr. Comp. Physiol. Publication Date: 2009 Jun |
Date Detail:
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Created Date: 2009-05-21 Completed Date: 2009-07-02 Revised Date: 2010-09-23 |
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: R1813-9 Citation Subset: IM |
Affiliation:
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Department of Physiology and Functional Genomics, PO Box 100274, University of Florida College of Medicine, Gainesville, FL 32610-0274, USA. woodc@ufl.edu |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Adrenocorticotropic Hormone
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blood Animals Baroreflex / drug effects Blood Pressure / drug effects Brachiocephalic Trunk / surgery Brain / blood supply, drug effects*, embryology Brain Ischemia / drug therapy*, embryology, enzymology, physiopathology Cerebrovascular Circulation / drug effects* Cyclooxygenase 2 / metabolism* Cyclooxygenase 2 Inhibitors / administration & dosage* Disease Models, Animal Fetal Blood / metabolism Gestational Age Heart Rate, Fetal / drug effects Homeostasis Hydrocortisone / blood Hypotension / drug therapy*, embryology, enzymology, physiopathology Hypothalamo-Hypophyseal System / drug effects*, metabolism Infusions, Parenteral Pituitary-Adrenal System / drug effects*, metabolism Pro-Opiomelanocortin / blood Sheep Sulfonamides / administration & dosage* |
| Grant Support | |
ID/Acronym/Agency:
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HD33053/HD/NICHD NIH HHS; HD42135/HD/NICHD NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Cyclooxygenase 2 Inhibitors; 0/Sulfonamides; 50-23-7/Hydrocortisone; 51803-78-2/nimesulide; 66796-54-1/Pro-Opiomelanocortin; 9002-60-2/Adrenocorticotropic Hormone; EC 1.14.99.1/Cyclooxygenase 2 |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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