Sj. Read et al., Effects of sumatriptan on nitric oxide and superoxide balance during glyceryl trinitrate infusion in the rat. Implications for antimigraine mechanisms, BRAIN RES, 847(1), 1999, pp. 1-8
Infusion of glyceryl trinitrate (GTN) into patients with migraine precipita
tes the onset of a migraine attack several hours after completion of the in
fusion. Using an infusion of GTN into anaesthetised rats, this study invest
igates the relationship of regional cerebral blood flux rCBF(ldf), cortical
nitric oxide (NO) and cortical superoxide concentrations and the effect of
sumatriptan on each variable. In saline treated animals, a 30 min infusion
of GTN (2 mu g kg(-1) min(-1), i.v.) was found to markedly increase cortic
al rCBF(ldf) (133 +/- 3% of baseline) and NO concentrations (141 +/- 13% of
baseline). Superoxide levels exhibited an inverse relationship to NO level
s, decreasing below basal to 48 +/- 14% of baseline. It is hypothesised tha
t high NO levels during GTN infusion may decrease the detectable superoxide
due to ''leeching'' of the superoxide into low level peroxynitrite formati
on. In the presence of sumatriptan, a decrease below baseline in cortical r
CBF(ldf) (82 +/- 5% of baseline) and NO concentration (64 +/- 13% of baseli
ne) was observed throughout GTN infusion, although superoxide levels signif
icantly increased above baseline by 105 +/- 14 nM (p < 0.05, ANOVA post hoc
LSD test). The mechanism for this action of sumatriptan is unknown but may
include; modulation of cell redox state, NO scavenging or direct manipulat
ion of superoxide release. (C) 1999 Elsevier Science B.V. All rights reserv
ed.