RGD Reference Report - Increased pulmonary prostacyclin synthesis in rats with chronic hypoxic pulmonary hypertension. - Rat Genome Database

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Increased pulmonary prostacyclin synthesis in rats with chronic hypoxic pulmonary hypertension.

Authors: Blumberg, Friedrich C  Lorenz, Cornelia  Wolf, Konrad  Sandner, Peter  Riegger, Günter A J  Pfeifer, Michael 
Citation: Blumberg FC, etal., Cardiovasc Res. 2002 Jul;55(1):171-7. doi: 10.1016/s0008-6363(02)00318-8.
RGD ID: 401959327
Pubmed: PMID:12062720   (View Abstract at PubMed)
DOI: DOI:10.1016/s0008-6363(02)00318-8   (Journal Full-text)


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.



RGD Manual Disease Annotations    Click to see Annotation Detail View
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
PTGISHumanPulmonary Hypertension, Hypoxia-Induced treatmentISOPtgis (Rattus norvegicus) RGD 
PtgisRatPulmonary Hypertension, Hypoxia-Induced treatmentIEP  RGD 
PtgisMousePulmonary Hypertension, Hypoxia-Induced treatmentISOPtgis (Rattus norvegicus) RGD 

Gene-Chemical Interaction Annotations    Click to see Annotation Detail View
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
PTGISHumandiatomic oxygen increases expression ISOPtgis (Rattus norvegicus)Hypoxia increases expression of Ptgis mRNA in the lungRGD 
PtgisRatdiatomic oxygen increases expression EXP Hypoxia increases expression of Ptgis mRNA in the lungRGD 
PtgisMousediatomic oxygen increases expression ISOPtgis (Rattus norvegicus)Hypoxia increases expression of Ptgis mRNA in the lungRGD 
PTGISHumanmolsidomine multiple interactionsISOPtgis (Rattus norvegicus)Molsidomine inhibits the reaction [Hypoxia increases expression of Ptgis mRNA in the lung]RGD 
PtgisRatmolsidomine multiple interactionsEXP Molsidomine inhibits the reaction [Hypoxia increases expression of Ptgis mRNA in the lung]RGD 
PtgisMousemolsidomine multiple interactionsISOPtgis (Rattus norvegicus)Molsidomine inhibits the reaction [Hypoxia increases expression of Ptgis mRNA in the lung]RGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
PtgisRatresponse to hypoxia  IEP  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Ptgis  (prostaglandin I2 synthase)

Genes (Mus musculus)
Ptgis  (prostaglandin I2 (prostacyclin) synthase)

Genes (Homo sapiens)
PTGIS  (prostaglandin I2 synthase)


Additional Information