| Increased pulmonary prostacyclin synthesis in rats with chronic hypoxic pulmonary hypertension. | |
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MedLine Citation:
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PMID: 12062720 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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OBJECTIVE: The regulation of pulmonary prostacyclin synthesis is not completely understood. We tested the hypothesis that prostacyclin production is predominantly stimulated by hemodynamic factors, such as increased shear-stress, and is thus increased in rats with chronic hypoxic pulmonary hypertension. METHODS: To this end, we determined pulmonary prostacyclin synthase (PGIS) gene expression, circulating levels of the stable prostacyclin metabolite 6-keto prostaglandin F(1alpha) (6-keto-PGF(1alpha)), pulmonary endothelin (ET)-1 gene expression, and ET-1 plasma levels in rats exposed to 4 weeks of hypoxia (10% O(2)) in the presence or absence of either the nitric oxide (NO) donor molsidomine (MD, 15 mg/kg/day) or the ET-A receptor antagonist LU135252 (LU, 50 mg/kg/day). RESULTS: Right ventricular systolic pressure (RVSP), the cross-sectional medial vascular wall area of pulmonary arteries, and ET-1 production increased significantly during hypoxia. PGIS mRNA levels increased 1.7-fold, and 6-keto-PGF(1alpha) plasma levels rose from 8.2+/-0.8 to 12.2+/-2.2 ng/ml during hypoxia (each P<0.05 vs. normoxic controls). MD and LU reduced RVSP and pulmonary vascular remodeling similarly (each P<0.05 vs. hypoxia), but only MD inhibited pulmonary ET-1 formation (P<0.05 vs. hypoxia). Nevertheless, both drugs attenuated the increase in PGIS gene expression and plasma 6-keto-PGF(1alpha) levels (each P<0.05 vs. hypoxia). CONCLUSION: Our data suggest that prostacyclin production in hypertensive rat lungs is predominantly increased by hemodynamic factors while hypoxia, NO and ET-1 per are less important stimuli, and that this increase may serve as a compensatory mechanism to partially negate the hypoxia-induced elevation in pulmonary vascular tone. |
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Authors:
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Friedrich C Blumberg; Cornelia Lorenz; Konrad Wolf; Peter Sandner; Günter A J Riegger; Michael Pfeifer |
Publication Detail:
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Type: Comparative Study; Journal Article |
Journal Detail:
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Title: Cardiovascular research Volume: 55 ISSN: 0008-6363 ISO Abbreviation: Cardiovasc. Res. Publication Date: 2002 Jul |
Date Detail:
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Created Date: 2002-06-13 Completed Date: 2002-09-06 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 0077427 Medline TA: Cardiovasc Res Country: Netherlands |
Other Details:
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Languages: eng Pagination: 171-7 Citation Subset: IM |
Affiliation:
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Department of Internal Medicine II, University of Regensburg, Germany. friedrich.blumberg@klinik.uni-regensburg.de |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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6-Ketoprostaglandin F1 alpha
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blood Animals Anoxia Chronic Disease Cytochrome P-450 Enzyme System / genetics Endothelin-1 / blood, genetics Hypertension, Pulmonary / blood, drug therapy*, pathology Intramolecular Oxidoreductases / genetics Male Models, Animal Molsidomine / therapeutic use* Nitric Oxide Donors / therapeutic use* Phenylpropionates / therapeutic use* Pulmonary Artery / metabolism, pathology Pyrimidines / therapeutic use* RNA, Messenger / analysis Random Allocation Rats Rats, Wistar Receptor, Endothelin A Receptors, Endothelin / antagonists & inhibitors* Systole Ventricular Pressure |
| Chemical | |
Reg. No./Substance:
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0/Endothelin-1; 0/LU 135252; 0/Nitric Oxide Donors; 0/Phenylpropionates; 0/Pyrimidines; 0/RNA, Messenger; 0/Receptor, Endothelin A; 0/Receptors, Endothelin; 25717-80-0/Molsidomine; 58962-34-8/6-Ketoprostaglandin F1 alpha; 9035-51-2/Cytochrome P-450 Enzyme System; EC 5.3.-/Intramolecular Oxidoreductases; EC 5.3.99.4/prostacyclin synthetase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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