Brief Article
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World J Cardiol. Oct 26, 2013; 5(10): 375-381
Published online Oct 26, 2013. doi: 10.4330/wjc.v5.i10.375
Migraine attack restores the response of vascular smooth muscle cells to nitric oxide but not to norepinephrine
Raffaele Napoli, Vincenzo Guardasole, Emanuela Zarra, Antonietta De Sena, Francesco Saccà, Antonio Ruvolo, Simona Grassi, Speranza Giugliano, Giovanna De Michele, Antonio Cittadini, Pietro Biagio Carrieri, Luigi Saccà
Raffaele Napoli, Vincenzo Guardasole, Emanuela Zarra, Antonietta De Sena, Antonio Ruvolo, Simona Grassi, Speranza Giugliano, Giovanna De Michele, Antonio Cittadini, Luigi Saccà, Department of Translational Medical Sciences, Federico II University School of Medicine, 80131 Naples, Italy
Francesco Saccà, Pietro Biagio Carrieri, Department of Neurology, Federico II University School of Medicine, 80131 Naples, Italy
Author contributions: Napoli R had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis; Napoli R, Carrieri PB and Saccà L studied concept and designed; Napoli R, Guardasole V, Zarra E, De Sena A, Saccà F, Ruvolo A, Grassi S, Giugliano S, De Michele G and Cittadini A did the experiments and acquisition of data; Napoli R, Carrieri PB and Saccà L did the analysis and interpretation of data; Napoli R and Saccà L did the drafting of the manuscript; Guardasole V, Zarra E, De Sena A, Saccà F, Ruvolo A, Grassi S, Giugliano S, De Michele G, Cittadini A and Carrieri PB made critical revision of the manuscript for important intellectual content; Napoli R and Saccà L performed statistical analysis; Napoli R and Saccà L did study supervision; all authors have read and approved the final version of the article.
Correspondence to: Raffaele Napoli, MD, Department of Translational Medical Sciences, Federico II University School of Medicine, Via Pansini 5, 80131 Napoli, Italy. napoli@unina.it
Telephone: +39-81-7463736 Fax: +39-81-7463198
Received: May 8, 2013
Revised: August 10, 2013
Accepted: September 13, 2013
Published online: October 26, 2013
Processing time: 169 Days and 23.8 Hours
Abstract

AIM: To clarify whether the vasoconstrictory response is impaired and to study vascular function in patients with migraine during the headache attack.

METHODS: We studied vascular reactivity in the resistance arteries by using the forearm perfusion technique associated with plethysmography. We measured forearm blood flow by strain-gauge plethysmography during intra-brachial infusion of acetylcholine, sodium nitroprusside or norepinephrine in 11 controls and 13 patients with migraine, 11 of them (M) in the interval between the migraine attacks and 4 during a headache attack (MH). Written informed consent was obtained from patients and healthy controls, and the study was approved by the Ethics Committee of the University Federico II.

RESULTS: Compared to healthy control subjects, in patients with migraine studied during the interictal period, the vasodilating effect of acetylcholine, that acts through the stimulation of endothelial cells and the release of nitric oxide, was markedly reduced, but became normal during the headache attack (P < 0.05 by analysis of variance). The response to nitroprusside, which directly relaxes vascular smooth muscle cells (VSMCs), was depressed in patients with migraine studied during the interictal period, but normal during the headache attack (P < 0.005). During norepinephrine infusion, forearm blood flow decreased in control subjects (-40% ± 5%, P < 0.001). In contrast, in patients with migraine, either when studied during or free of the headache attack forearm blood flow did not change compared to the baseline value (-3% ± 13% and -10.4% ± 15%, P > 0.05).

CONCLUSION: In migrainers, the impaired relaxation of VSMCs is restored during the headache attack. The vasoconstrictory response is impaired and remains unchanged during the migraine attack.

Keywords: Migraine; Nitric oxide; Endothelium; Vascular smooth muscle cells

Core tip: Patients with migraine without aura studied in the interictal period are characterized by impaired ability of vascular smooth muscle cells (VSMCs) to relax in response to nitric oxide and to contract in response to norepinephrine. We hypothesize that the two defects compensate for each other and this provides for the maintenance of normal vascular resistance and blood pressure homeostasis. In contrast, during the headache attack, the VSMCs regain their ability to respond to nitric oxide, but remain unresponsive to norepinephrine. Such differential effect of the migraine attack is not surprising, given that nitric oxide and norepinephrine activate different intracellular signaling pathways in VSMCs.