ANTIANGINAL EFFECTS OF FR144420, A NOVEL SLOW NITRIC OXIDE-RELEASING AGENT

The aim of this study was to compare the antianginal effects of two co mpounds that release nitric oxide (NO) spontaneously, i.e. oxyimino]-5 -nitro-3-hexenyl]-3-pyridinecarboxamide (FR144420) and E)-ethyl-2-[(E) -hydroxyimino]-5-nitro-3-hexenamide (FK409), in two different rat mode ls of coronary vasospasm. In the rat methacholine-induced coronary vas ospasm model, FR144420 suppressed the elevation of the ST segment dose dependently and significantly at 1.0 mg/kg, i.d. 185 min after its ad ministration. FK409 suppressed the ST elevation only 5 min after its a dministration at 1.0 mg/kg, i.d. FR144420 and FK409 significantly decr eased mean blood pressure at all doses tested only 5 min after their i ntraduodenal administration, but did not change heart rate at any time . Although the suppression of the ST elevation by FK409 had the same d uration as its hypotensive effect, the FR144420-induced suppression of the ST elevation lasted longer than its hypotensive effect. In the ra t vasopressin-induced coronary vasospasm model, FR144420 (32 mg/kg) si gnificantly inhibited the depression of the ST segment both 60 min and 120 min after oral administration, whereas FK409 (32 mg/kg) significa ntly inhibited this ST depression only 60 min after oral administratio n. These data suggest that FR144420 inhibits coronary vasospasm for lo nger than FK409 does and particularly shows more prolonged antianginal effects than hypotensive effects in the methacholine-induced coronary vasospasm model. Thus FR144420 is expected to be a useful NO releaser for investigating the in vivo actions of NO.