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Antiplatelet activities of FK409, a new spontaneous NO releaser
Author(s) -
Kita Yasuhiro,
Hirasawa Yoshimi,
Yoshida Keizo,
Maeda Kazuhiro
Publication year - 1994
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1994.tb17000.x
Subject(s) - in vivo , chemistry , pharmacology , nitric oxide , in vitro , platelet , integrated services digital network , medicine , biochemistry , biology , electrical engineering , engineering , microbiology and biotechnology , organic chemistry
1 We reported that (±)‐(E)‐ethyl‐2‐[(E)‐hydroxyimino]‐5‐nitro‐3‐hexeneamide (FK409) released nitric oxide (NO) spontaneously with a chemiluminescence analyzer. The aim of this study was to compare antiplatelet activities of FK409, a new NO releaser, with those of isosorbide dinitrate (ISDN) in vivo and in vitro . In order to elucidate the differences in antiplatelet activities between FK409 and ISDN, we compared their modes of action. 2 In in vitro experiments, FK409 had a more potent inhibitory effect on rat platelet aggregation induced by adenosine 5′‐diphosphate (2.0 μ m ) than ISDN (IC 50 = 4.32 ± 0.95μ m and > 100 μ m respectively). 3 In the rat extracorporeal shunt model ( in vivo experiments), FK409 suppressed thrombus formation dose‐dependently from 0.32 mg kg ‐1 , p.o. and showed the maximum inhibition (52% inhibition vs. vehicle treatment) at 10 mg kg ‐1 , p.o., while ISDN showed no inhibition at 10 mg kg ‐1 and only 17% inhibition at 32 mg kg ‐1 , p.o. 4 FK409 could generate nitrite, which is an oxidative product of NO, much faster than ISDN in phosphate buffer solution and rat plasma during 60‐min incubation at 37°C. 5 These data show that FK409 has more potent antiplatelet effects than ISDN, by acting through spontaneously released NO.