Vascular smooth muscle cell dysfunction in patients with migraine

Neurology. 2009 Jun 16;72(24):2111-4. doi: 10.1212/WNL.0b013e3181aa53ce.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholine / pharmacology
  • Adult
  • Blood Pressure / drug effects
  • Blood Pressure / physiology
  • Brachial Artery / drug effects
  • Brachial Artery / metabolism
  • Brachial Artery / physiopathology
  • Cardiovascular Diseases / complications
  • Cardiovascular Diseases / metabolism*
  • Cardiovascular Diseases / physiopathology*
  • Case-Control Studies
  • Comorbidity
  • Cyclic GMP / metabolism
  • Endothelial Cells / drug effects
  • Endothelial Cells / metabolism
  • Female
  • Hemodynamics / drug effects
  • Hemodynamics / physiology
  • Humans
  • Male
  • Migraine Disorders / complications
  • Migraine Disorders / metabolism*
  • Migraine Disorders / physiopathology*
  • Muscle, Smooth, Vascular / drug effects
  • Muscle, Smooth, Vascular / metabolism*
  • Muscle, Smooth, Vascular / physiopathology*
  • Nitric Oxide / metabolism
  • Nitroprusside / pharmacology
  • Regional Blood Flow / drug effects
  • Regional Blood Flow / physiology
  • Vasoconstriction / drug effects
  • Vasoconstriction / physiology
  • Vasodilation / drug effects
  • Vasodilation / physiology
  • Vasodilator Agents / pharmacology

Substances

  • Vasodilator Agents
  • Nitroprusside
  • Nitric Oxide
  • Cyclic GMP
  • Acetylcholine