The effect of nitric oxide synthase inhibition on histamine induced headache and arterial dilatation in migraineurs

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We have previously proposed that histamine causes migraine via increased NO production. To test this hypothesis, we here examined if the NOS inhibitor, L-NG methylarginine hydrochloride (L-NMMA:546C88), could block or attenuate histamine induced migraine attacks and responses of the middle cerebral, temporal and radial arteries. In a double blind crossover design 12 patients were randomized to receive pretreatment with L-NMMA (6 mg/kg) or placebo i.v. over 15 min followed on both study days by histamine (0.5 microg/kg/min) i.v. for 20 min. Headache scores, mean maximal blood velocity (Vmean) in the middle cerebral artery (MCA) (transcranial doppler) and diameters of temporal and radial arteries (high resolution ultrasound) were repeatedly measured. Pre-treatment with L-NMMA, had no effect on histamine induced headache or migraine, but also had no effect on the magnitude of histamine induced-decrease in MCA blood velocity, or dilatation of neither the temporal nor the radial artery. L-NMMA constricted the temporal artery by 8% before histamine infusion, whereas the radial artery was unaffected. The temporal artery dilated 4-5 times more than the radial artery during histamine infusion. In conclusion the use of a NOS inhibitor in the highest possible dose did not block the histamine-induced headache response or arterial dilatation. Either the concentration of L-NMMA reaching the smooth muscle cell was insufficient or, histamine dilates arteries and causes headache via NO independent mechanisms. Our results showed for the first time a craniospecificity for the vasodilating effect of histamine and for the arterial effects of NOS inhibition.

Original languageEnglish
JournalCephalalgia : an international journal of headache
Issue number9
Pages (from-to)877-86
Number of pages10
Publication statusPublished - Nov 2003

    Research areas

  • Adult, Blood Pressure, Cerebral Arteries, Cerebrovascular Circulation, Cross-Over Studies, Double-Blind Method, Enzyme Inhibitors, Female, Histamine, Humans, Male, Middle Aged, Migraine Disorders, Nitric Oxide, Nitric Oxide Synthase, Organ Culture Techniques, Radial Artery, Time Factors, Vasodilation, omega-N-Methylarginine

ID: 128983591