Nilvadipine inhibits nuclear factor-kappaB-dependent transcription in hepatic cells.
BACKGROUND
Recent findings suggest that some dihydropyridine-type calcium channel blockers, widely used as anti-hypertensive drugs, have direct anti-atherogenic action through their antioxidant properties.


METHODS
We examined the effect of nilvadipine on the activity of a representative radical-sensitive transcription factor, nuclear factor kappa-B (NF-kappaB), in the human hepatocyte cell line HuH7 in vitro.


RESULTS
Nilvadipine potently inhibited NF-kappaB-dependent transcription in a dose- and time-dependent manner, with a minimal effective concentration of 50 nmol/l. The effect was specific because no similar effects were found in the prototype dihydropyridine nifedipine. Electromobility shift assay showed reduced protein binding to the NF-kappaB-consensus sequence in nilvadipine-treated cells. Nilvadipine also reduced the expression of fibrinogen and plasminogen activator inhibitor-1 (PAI-1).


CONCLUSIONS
Since NF-kappaB-mediated gene products, such as fibrinogen and PAI-1, are known to facilitate hypercoagulation, thrombosis and vascular events, we suggest that nilvadipine has a direct beneficial effect separate from its anti-hypertensive properties by inhibiting NF-kappaB-dependent gene expression and eventually inhibiting atherosclerosis.
Iwasaki
Yasumasa
Y
Department of Clinical Pathophysiology, Nagoya University Graduate School of Medicine and Hospital, Nagoya 466-8550, Japan. iwasaki@med.kochi-u.ac.jp
Asai
Masato
M
Yoshida
Masanori
M
Nigawara
Takeshi
T
Kambayashi
Machiko
M
Oiso
Yutaka
Y
Nakashima
Nobuo
N
D001161:Arteriosclerosis / Q000188:drug therapy; D001483:Base Sequence; D004586:Electrophoresis / Q000379:methods; D005340:Fibrinogen / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D022781:Hepatocytes / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D016328:NF-kappa B / Q000378:metabolism*; D009543:Nifedipine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism; D013997:Time Factors; D051996:Transcription Factor RelA; D014158:Transcription, Genetic / Q000187:drug effects*
D016328:NF-kappa B; D017395:Plasminogen Activator Inhibitor 1; D051996:Transcription Factor RelA; C035100:nilvadipine; D005340:Fibrinogen; D009543:Nifedipine