The Effect of Nitric Oxide Synthase Inhibition on Histamine Induced Headache and Arterial Dilatation in Migraineurs

Abstract

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.

Intravenously Administered Histamine Increases Choroidal but not Retinal Blood Flow

“…In a recent study a decrease in blood speed in the middle cerebral artery, together with vasodilatation in the temporal and radial arteries, was found after histamine infusion. 26 This effect is compatible with the decreased retinal blood speed and increased vessel diameters found in retinal branch veins in this study.…”

Association of the long pentraxin PTX3 gene polymorphism (rs3816527) with migraine in an Iranian population

“…On the other hand several studies demonstrated the key role of inflammatory cytokines in pathophysiology of migraine. These studies showed that serum level of inflammatory cytokines such as IL-1beta and TNF-α and also NO was higher in patients with migraine compared to healthy controls [4,22]. Furthermore, migraine could be considered as a vascular disease and PTX3 like CRP, is independently associated with the risk of developing vascular events [23,24].…”

Nitric Oxide-Related Drug Targets in Headache

“…15 Similarly, Lassen et al 16 have reported that L-NMMA produced: 1) a 20% increase in blood pressure with a concomitant 24% decrease in heart rate at the maximal dose; 2) a 6.8% decrease in brain blood flow; and 3) no effect on acetazolamide-induced increase in cerebral blood flow. These results suggest that there is no basal NO tone in human cerebral arteries, but that there is a mild dilator tone in cerebral (and systemic) arterioles regulating blood flow and blood pressure.…”