Coupling factor 6-induced prostacyclin inhibition is enhanced in vascular smooth muscle cells from spontaneously hypertensive rats.
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.
Osanai
Tomohiro
T
Department of Cardiology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan. osanait@cc.hirosaki-u.ac.jp
Tomita
Hirofumi
H
Yamada
Masahiro
M
Tanaka
Makoto
M
Ashitate
Toshihiro
T
Echizen
Takashi
T
Katoh
Chisato
C
Magota
Koji
K
Okumura
Ken
K
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
D010086:Oxidative Phosphorylation Coupling Factors; D011464:Epoprostenol; C000628217:F(6) ATPase; D025261:Mitochondrial Proton-Translocating ATPases