Endothelin-1 secretion from cultured vascular endothelial cells of DOCA-salt hypertensive rats.
The profile of endothelin-1 (ET-1) release from cultured vascular endothelial cells (ECs) obtained from deoxycorticosterone acetate (DOCA)-salt hypertensive rats, was examined and compared with that from normotensive sham rats. ET-1 release from ECs was increased in a time-dependent manner, and the level of DOCA-salt hypertensive rats was higher than that of sham rats. Incubation of ECs with transforming growth factor (TGF)-beta 1 or thrombin resulted in a significant increase in the ET-1 release, while FK409, a novel nitric oxide donor, produced a dose-dependent decrease in the release. In the case of ECs from DOCA-salt hypertensive rats, the potencies of TGF-beta 1- or thrombin-induced action was much less than that seen with sham rats, while the difference of reactivity to FK409 was not observed between ECs of DOCA-salt rats and sham rats. Thus, ET-1 production in ECs appears to be up-regulated in DOCA-salt hypertensive rats. In addition, there seems to be an abnormalities in the signaling pathway via TGF-beta 1- or thrombin-induced enhancement of ET-1 production in ECs of DOCA-salt hypertensive rats.
Takada
K
K
Department of Pharmacology, Osaka University of Pharmaceutical Sciences, Japan.
Matsumura
Y
Y
Dohmen
S
S
Mitsutomi
N
N
Takaoka
M
M
Morimoto
S
S
D000818:Animals; D001011:Aorta; D002478:Cells, Cultured; D003900:Desoxycorticosterone; D016232:Endothelins / Q000096:biosynthesis*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D006973:Hypertension / Q000139:chemically induced / Q000503:physiopathology*; D007700:Kinetics; D008297:Male; D009574:Nitro Compounds / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D012965:Sodium Chloride; D013917:Thrombin / Q000494:pharmacology*; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D014665:Vasodilator Agents / Q000494:pharmacology
D016232:Endothelins; D009574:Nitro Compounds; D016212:Transforming Growth Factor beta; D014665:Vasodilator Agents; D003900:Desoxycorticosterone; D012965:Sodium Chloride; C061872:FK 409; D013917:Thrombin