title: Coupling factor 6-induced prostacyclin inhibition is enhanced in vascular smooth muscle cells from spontaneously hypertensive rats.
abstract: OBJECTIVE
  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).
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Cardiology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan. osanait@cc.hirosaki-u.ac.jp
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Osanai
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Tomita
authors.forename: Masahiro
authors.initials: M
authors.lastname: Yamada
authors.forename: Makoto
authors.initials: M
authors.lastname: Tanaka
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Ashitate
authors.forename: Takashi
authors.initials: T
authors.lastname: Echizen
authors.forename: Chisato
authors.initials: C
authors.lastname: Katoh
authors.forename: Koji
authors.initials: K
authors.lastname: Magota
authors.forename: Ken
authors.initials: K
authors.lastname: Okumura
mesh_terms: D000818:Animals; D019898:Autocrine Communication; D002478:Cells, Cultured; D011464:Epoprostenol / Q000096:biosynthesis*; D006973:Hypertension / Q000378:metabolism*; D008297:Male; D008638:Mesenteric Arteries / Q000166:cytology / Q000378:metabolism; D025261:Mitochondrial Proton-Translocating ATPases / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000378:metabolism*; D010086:Oxidative Phosphorylation Coupling Factors / Q000378:metabolism*; D019899:Paracrine Communication; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY
chemical_list: D010086:Oxidative Phosphorylation Coupling Factors; D011464:Epoprostenol; C000628217:F(6) ATPase; D025261:Mitochondrial Proton-Translocating ATPases