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Abstract
The effect of FK409, a new nitric-oxide (NO) donor, on neointimal formation of rat
carotid arteries following balloon injury was studied. The intimal thickening at 14
days was strongly suppressed by twice daily administration of FK409 at 10 mg/kg from
2 days before to 13 days after injury. The neointima area and neointima/media ratio
were decreased by 48.0% (P < 0.01) and 38.5% (P < 0.01), respectively, compared with control. On the other hand, isosorbide dinitrate
(ISDN), a classical nitro-vasodilator, did not suppress intimal thickening even at
100 mg/kg twice a day. An in vivo 5-bromo-2′-deoxyuridine (BrdU) uptake study revealed
that FK409 inhibited the proliferative response of smooth muscle cells (SMC) in media
at early stage of injury. In fact, the neointimal formation at 14 days was inhibited
by the short term administration of FK409 only from the day of injury to 4 days after
at 10 mg/kg twice a day. In cultured rat SMC, FK409 (1–10 μmol/l) markedly enhanced
intracellular c-GMP and inhibited the proliferation in 10% FBS-containing medium.
These results suggest that FK409 suppresses intimal thickening following balloon injury
of the rat carotid artery by inhibition of SMC proliferation.
Keywords
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Article info
Publication history
Accepted:
March 13,
1995
Received in revised form:
March 7,
1995
Received:
November 30,
1994
Identification
Copyright
© 1995 Published by Elsevier Inc.
