RGD Reference Report - Coupling factor 6-induced prostacyclin inhibition is enhanced in vascular smooth muscle cells from spontaneously hypertensive rats. - Rat Genome Database

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Coupling factor 6-induced prostacyclin inhibition is enhanced in vascular smooth muscle cells from spontaneously hypertensive rats.

Authors: Osanai, Tomohiro  Tomita, Hirofumi  Yamada, Masahiro  Tanaka, Makoto  Ashitate, Toshihiro  Echizen, Takashi  Katoh, Chisato  Magota, Koji  Okumura, Ken 
Citation: Osanai T, etal., J Hypertens. 2009 Sep;27(9):1823-8. doi: 10.1097/HJH.0b013e32832d4b05.
RGD ID: 13800898
Pubmed: PMID:19474762   (View Abstract at PubMed)
DOI: DOI:10.1097/HJH.0b013e32832d4b05   (Journal Full-text)


OBJECTIVES: Coupling factor 6 (CF6) attenuates the endothelial generation of prostacyclin. However, the role of CF6 in the resistance arteriole that is directly related to vascular tone is not determined yet. We investigated the effect of endogenous and exogenous CF6 on prostacyclin generation in cultured vascular smooth muscle cells (VSMCs).
METHODS AND RESULTS: We cultured resistance arteriole VSMCs from the mesenteric artery network of spontaneously hypertensive rats (SHRs, n = 8) and Wistar-Kyoto rats (WKY, n = 8) by enzymatic method. The gene expression of CF6 was higher by 76 +/- 24% in SHR-derived VSMCs compared with WKY rat-derived VSMCs (P < 0.05) concomitant with the reduced degradation rate of CF6 mRNA. The release of CF6 in SHRs was higher than that in WKY rats (11.0 +/- 0.8 vs. 3.8 +/- 0.4 pg/microg protein, P < 0.05). Prostacyclin generation was attenuated in mesenteric arteriolar VSMCs from SHRs compared with those from WKY rats, but it was restored by neutralization of CF6 with its antibody. Exogenous administration of CF6 suppressed arachidonic acid release in a dose-dependent manner, and it was greater in SHRs than in WKY rats. Pretreatment with PP1, an inhibitor of tyrosine kinase c-Src, or receptor blockers such as ADP, efrapeptin, and an antibody to beta-subunit of ATP synthase blocked CF6-induced decrease in prostacyclin generation.
CONCLUSION: These data suggest that CF6 suppresses prostacyclin generation in resistance arteriole VSMCs in an autocrine or paracrine fashion, and it is enhanced in SHRs by the overproduction of CF6 and the hyperresponsiveness to CF6.



Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Atp5pfRatnegative regulation of prostaglandin secretion  IMP  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Atp5pf  (ATP synthase peripheral stalk subunit F6)


Additional Information