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Soluble guanylate cyclase induces cranial vasodilation and headache in adults: a randomized trial

Rasmussen NB, Christensen CE, Ashina H, Amin FM, Domínguez-Moreno R, Abdulla J, Carlsen J, Ashina M

Brain communications, 2025

12 participants · 1 citation

Abstract

The role of cranial vasodilation in headache pathogenesis sparks ongoing debate. Soluble guanylate cyclase is an enzyme that catalyses the conversion of guanosine triphosphate to cyclic guanosine monophosphate, leading to relaxation of vascular smooth muscle cells. Activation of this pathway might contribute to headache pathogenesis. We evaluated whether oral ingestion of riociguat, a stimulator of soluble guanylate cyclase, could elicit cranial vasodilation and headache in healthy adults. In this randomized, double-blind, placebo-controlled, two-way crossover study, we enrolled 12 healthy adults (nine females, three males; mean age 27.3 (SD 7.8) years). The participants attended two experimental sessions at a single site in Denmark (Danish Headache Center, Rigshospitalet, Denmark), receiving either a single oral dose riociguat 2.5 mg or placebo. The baseline measurements included the diameter of the superficial temporal artery and the blood flow velocity of the middle cerebral artery. These measurements were repeated over a 240-minute period after ingestion. The participants recorded headache occurrence and associated features in a diary for 12 h post-ingestion. For primary outcome (n = 12), results revealed no significant change in the diameter of the superficial temporal artery from baseline to 90 min post-ingestion between riociguat and placebo (P = 0.54). However, significant increases in the diameter were observed at 120 min (P = 0.02) and 240 min (P P P = 0.02). In…

How strong is the evidence?

Evidence Hub reads this as a randomized trial, done in people. Its evidence level is 3 of 5 (Moderate · trial / cohort / secondary analysis). Trials without a large randomized design, cohorts and secondary analyses give moderate evidence. Reported size: 12 participants or records.

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