RGD Reference Report - A long-acting prostacyclin agonist with thromboxane inhibitory activity for pulmonary hypertension. - Rat Genome Database

Send us a Message
Submit Data |  Help |  Video Tutorials |  News |  Publications |  Download |  REST API |  Citing RGD |  Contact   
Search RGD Grant Resources Citing RGD About Us Contact Us
Genes Variants Community Projects QTLs Strains Markers Genome Information Ontologies Cell Lines References Download Submit Data
OntoMate (Literature Search) JBrowse (Genome Browser) Synteny Browser (VCMap) Variant Visualizer Multi-Ontology Enrichment (MOET) Gene-Ortholog Location Finder (GOLF) InterViewer (Protein-Protein Interactions) PhenoMiner (Quatitative Phenotypes) Gene Annotator OLGA (Gene List Generator) AllianceMine GViewer (Genome Viewer)
Aging & Age-Related Disease Cancer & Neoplastic Disease Cardiovascular Disease Coronavirus Disease Developmental Disease Diabetes Hematologic Disease Immune & Inflammatory Disease Infectious Disease Liver Disease Neurological Disease Obesity & Metabolic Syndrome Renal Disease Respiratory Disease Sensory Organ Disease
Find Models   new Genetic Models Autism Models Rat PhenoMiner (Quantitative Phenotypes) Chinchilla PhenoMiner Expected Ranges (Quantitative Phenotype) PhenoMiner Term Comparison Hybrid Rat Diversity Panel Phenotypes Phenotypes in Other Animal Models Animal Husbandry Strain Medical Records Phylogenetics Strain Availability Calendar Rats 101 Submissions Photo Archive
Pathways
Rat Community Forum Directory of Rat Laboratories Video Tutorials News RGD Publications RGD Presentations Archive Nomenclature Guidelines Resource Links Laboratory Resources Employment Resources

A long-acting prostacyclin agonist with thromboxane inhibitory activity for pulmonary hypertension.

Authors: Kataoka, M  Nagaya, N  Satoh, T  Itoh, T  Murakami, S  Iwase, T  Miyahara, Y  Kyotani, S  Sakai, Y  Kangawa, K  Ogawa, S 
Citation: Kataoka M, etal., Am J Respir Crit Care Med. 2005 Dec 15;172(12):1575-80. Epub 2005 Sep 28.
RGD ID: 1601439
Pubmed: PMID:16192456   (View Abstract at PubMed)
DOI: DOI:10.1164/rccm.200501-102OC   (Journal Full-text)

RATIONALE: The balance between prostacyclin and thromboxane plays an important role in the regulation of pulmonary vascular tone. Recently, we developed ONO-1301, a novel, long-acting prostacyclin agonist with thromboxane synthase inhibitory activity. OBJECTIVES: We investigated whether modulation of prostacyclin/thromboxane balance by ONO-1301 ameliorates monocrotaline-induced pulmonary hypertension in rats. METHODS: After subcutaneous injection of monocrotaline or vehicle, rats were randomized to receive repeated subcutaneous administration of ONO-1301 or vehicle twice per day for 3 wk. MEASUREMENTS AND MAIN RESULTS: There was significant development of pulmonary hypertension 3 wk after monocrotaline injection. Treatment with ONO-1301 significantly attenuated the increases in right ventricular systolic pressure and ratio of right ventricular weight to body weight in monocrotaline rats. Furthermore, ONO-1301 significantly attenuated the increase in medial wall thickness of peripheral pulmonary arteries in monocrotaline rats. The half-life of plasma ONO-1301 concentration after a single subcutaneous administration was approximately 5.6 h. A single administration of ONO-1301 increased plasma cyclic adenosine 3', 5'-monophosphate level, which lasted at least up to 8 h. Treatment with ONO-1301 significantly decreased plasma 11-dehydro-thromboxane B2, a metabolite of thromboxane, in monocrotaline rats. Finally, Kaplan-Meier survival curves demonstrated that repeated administration of ONO-1301 improved survival rate in monocrotaline rats compared with vehicle administration (80 vs. 30% in 6-wk survival). CONCLUSIONS: Subcutaneous administration of a novel prostacyclin agonist (ONO-1301) markedly attenuated monocrotaline-induced pulmonary hypertension and improved survival in rats. The beneficial effects of ONO-1301 may occur through its long-lasting stimulation of cyclic adenosine 3', 5'-monophosphate and inhibition of thromboxane synthase.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
hypertension  ISOTbxas1 (Rattus norvegicus)1601439; 1601439 RGD 
hypertension  IDA 1601439 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Tbxas1  (thromboxane A synthase 1)

Genes (Mus musculus)
Tbxas1  (thromboxane A synthase 1, platelet)

Genes (Homo sapiens)
TBXAS1  (thromboxane A synthase 1)


Additional Information