RGD Reference Report - Effects of selective and unselective endothelin-receptor antagonists on prostacyclin synthase gene expression in experimental pulmonary hypertension. - Rat Genome Database

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Effects of selective and unselective endothelin-receptor antagonists on prostacyclin synthase gene expression in experimental pulmonary hypertension.

Authors: Schroll, S  Arzt, M  Sebah, D  Stoelcker, B  Luchner, A  Budweiser, S  Blumberg, F C  Pfeifer, M 
Citation: Schroll S, etal., Scand J Clin Lab Invest. 2008;68(4):270-6. doi: 10.1080/00365510701673375.
RGD ID: 401901264
Pubmed: PMID:18612919   (View Abstract at PubMed)
DOI: DOI:10.1080/00365510701673375   (Journal Full-text)


OBJECTIVE: Compared to the unselective endothelin (ET) receptor antagonist (Bosentan), superior effects of selective ET-A-receptor blockage (Ambrisentan) for the treatment of pulmonary hypertension (PH) are expected due to ET-B-receptor mediated beneficial effects. Our hypothesis was that treatment with Ambrisentan leads to an increase in prostacyclin synthase I (PGIS) expression compared to Bosentan.
MATERIAL AND METHODS: To test this hypothesis, rats were treated with either monocrotaline (MCT) only, MCT+Ambrisentan or MCT+Bosentan. After 4 weeks, right ventricular systolic pressure (RVSP), pulmonary vascular remodelling and right ventricular hypertrophy (RV/(LV+S)) were measured.
RESULTS: In MCT only treated animals, significantly greater expression of PGIS mRNA was found in the lungs compared to control animals, and this was confirmed by immunohistochemical analysis indicating increased staining of PGIS in the very small pulmonary arteries (17 % greater expression of PGIS mRNA in MCT versus control, p = 0.002; Remmele score (RS): 51 versus 102, p = 0.009). Treatment with Bosentan resulted in a significantly lower expression of PGIS mRNA compared to Ambrisentan and MCT only (7 % versus 18 %, p = 0.003 and 7 % versus 17 %, p = 0.004). This observation was also confirmed by immunohistochemical analysis (RS very small arteries: 45 versus 81, p = 0.003; RS small arteries: 45 versus 108, p = 0.014). No difference was observed in RVSP, RV/(LV+S) or pulmonary vascular remodelling between the two treatment groups (RVSP: 28 versus 39 mmHg, p = 0.189; RV/(LV+S) 0.46 versus 0.48, p = 0.818; medial area: 78.3 % versus 75.2 %, p = 0.823).
CONCLUSIONS: Treatment with Bosentan leads to lower PGIS expression in pulmonary arteries compared to Ambrisentan, although the greater PGIS expression by Ambrisentan treatment had no benefical effect on pulmonary haemodynamics.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
PTGISHumanPulmonary Arterial Hypertension treatmentISOPtgis (Rattus norvegicus) RGD 
PtgisRatPulmonary Arterial Hypertension treatmentIEP  RGD 
PtgisMousePulmonary Arterial Hypertension treatmentISOPtgis (Rattus norvegicus) RGD 

Gene-Chemical Interaction Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
PTGISHumanbosentan multiple interactionsISOPtgis (Rattus norvegicus)Bosentan inhibits the reaction [Monocrotaline increases expression of Ptgis mRNA in lung]RGD 
PtgisRatbosentan multiple interactionsEXP Bosentan inhibits the reaction [Monocrotaline increases expression of Ptgis mRNA in lung]RGD 
PtgisMousebosentan multiple interactionsISOPtgis (Rattus norvegicus)Bosentan inhibits the reaction [Monocrotaline increases expression of Ptgis mRNA in lung]RGD 
PTGISHumanmonocrotaline increases expression ISOPtgis (Rattus norvegicus)Monocrotaline increases expression of Ptgis mRNA in lungRGD 
PtgisRatmonocrotaline increases expression EXP Monocrotaline increases expression of Ptgis mRNA in lungRGD 
PtgisMousemonocrotaline increases expression ISOPtgis (Rattus norvegicus)Monocrotaline increases expression of Ptgis mRNA in lungRGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
PtgisRatresponse to alkaloid  IEP monocrotalineRGD 
PtgisRatresponse to organic cyclic compound  IEP BosentanRGD 

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