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© 2009 American Academy of Neurology Vascular smooth muscle cell dysfunction in patients with migraineFrom the Departments of Internal Medicine and Cardiovascular Sciences (R.N., V.G., E.Z., M.M., C.D., F.A., A.C., L.S.) and Neurology (F.S., P.B.C.), University Federico II School of Medicine, Naples, Italy. Address correspondence and reprint requests to Dr. Raffaele Napoli, Medicina Interna, Via Pansini 5, 80131 Napoli, Italy napoli{at}unina.it. Background: Migraine is associated with increased risk of cardiovascular disease, but the mechanisms are unclear. Objective: To investigate the activity of endothelial and vascular smooth muscle cells (VSMCs) in patients with migraine. Methods: Case-control study of 12 patients with migraine without aura and 12 matched healthy control subjects. Endothelial and VSMC components of vascular reactivity were explored by plethysmography measurement of forearm blood flow (FBF) during infusions of vasoactive agents into the brachial artery. Forearm production of nitric oxide (NO) and cyclic guanosine monophosphate (cGMP) was also quantified. Results: In patients with migraine, the vasodilating effect of acetylcholine (ACh), an endothelium-dependent vasodilator, was markedly reduced (p < 0.001 by analysis of variance). In response to the highest dose of ACh, FBF rose to 8.6 ± 2.2 in patients with migraine and to 22.7 ± 3.0 mL x dL–1 x min–1 in controls (p = 0.001). The dose-response curve to nitroprusside, a vasodilator directly acting on VSMCs, was depressed in patients with migraine (p < 0.001 by analysis of variance). The maximal response of FBF to nitroprusside was 12.1 ± 2.0 in patients with migraine and 24.1 ± 1.8 mL x dl–1 x min–1 in controls (p < 0.001). During ACh infusion, NO release from the endothelium was similar in patients and controls. In contrast, there was a marked release of cGMP from VSMCs in controls, but not in patients with migraine (–1.9 ± 2.2 in patients with migraine and –19.1 ± 5.4 nmol x dL–1 x min–1 in controls; p = 0.03). Conclusions: Patients with migraine are characterized by a distinct vascular smooth muscle cell dysfunction, revealed by impaired cyclic guanosine monophosphate and hemodynamic response to nitric oxide.
Abbreviations: ACh = acetylcholine; ADMA = asymmetric dimethylarginine; BMI = body mass index; cGMP = cyclic guanosine monophosphate; DBP = diastolic blood pressure; FBF = forearm blood flow; HR = heart rate; NO = nitric oxide; NP = nitroprusside; SBP = systolic blood pressure; VSMC = vascular smooth muscle cell.
Disclosure: Drs. Napoli and Saccà each received compensation for a clinical study (10% effort) from Pfeizer Italia. Medical Devices: Centricon 10 (Millipore, Bedford, MA); colorimetric kit (Cayman Chemical Co., Ann Arbor, MI); plethysmograph (Hokanson 045 EC4, P.M.S. Instruments, Berks, UK); radioimmunoassay (Amersham International, Amersham, UK). Received January 8, 2009. Accepted in final form March 16, 2009. This article has been cited by other articles:
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