Endothelin-1 enhances nitric oxide-induced cell death in cultured vascular smooth-muscle cells.
Increased expression of endothelin-1 (ET-1) immunoreactivity is demonstrated in the active atherosclerotic plaque. Here we show that both ETA and ETB receptors are expressed in rat vascular smooth-muscle cells (VSMCs). ET-1 binding to ETB receptors enhances nitric oxide-induced cell death in VSMCs. These findings suggest that ET-1 may participate in the mechanism of cell death (apoptosis) in the plaque through activation of ETB-mediated pathways and that a selective ETB receptor antagonist could be useful in preventing acute plaque alterations, such as plaque rupture.
Nakahashi
T
T
Department of Geriatric Medicine, Osaka University Medical School, Japan.
Fukuo
K
K
Nishimaki
H
H
Hata
S
S
Shimizu
M
M
Suhara
T
T
Takimoto
M
M
Morimoto
S
S
Ogihara
T
T
D000595:Amino Acid Sequence; D000818:Animals; D001013:Aorta, Thoracic / Q000166:cytology / Q000187:drug effects; D015153:Blotting, Western; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D004247:DNA / Q000378:metabolism; D019332:Endothelin-1 / Q000494:pharmacology*; D066298:In Vitro Techniques; D008969:Molecular Sequence Data; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000187:drug effects; D009569:Nitric Oxide / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin / Q000378:metabolism
D019332:Endothelin-1; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin; D009569:Nitric Oxide; D004247:DNA