Effects of sumatriptan on nitric oxide and superoxide balance during glyceryl trinitrate infusion in the rat. Implications for antimigraine mechanisms

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.