Differential vasoactive effects of sildenafil and tadalafil on cerebral arteries –relevant to migraine?
Abstract
BackgroundPhosphodiesterase 5 (PDE5) is associated with migrainepathophysiology, stroke recovery and vasospasm treat-ment [1,2]. We have shown previously that vasodilata-tion was not a prerequisite for migraine induction;sildenafil elicited migraine-like attacks in migrainepatients without measurable changes in intra- or extra-cerebral artery diameter. Further, sildenafil was found tonot affect neurovascular response or excitability [3].However, dural artery responses were not accounted forin the human studies and minor vascular changes offunctional importance may not have been detected.The potential vascular interplay of PDE5 inhibitors sil-denafil, tadalafil and UK-114,542 were studied by intra-versus extra-luminal administration in rat middle cere-bral arteries (MCA) in vitro and on middle meningealarteries (MMA) in vivo.AimTo examine a possible vascular site of action, if any, ofeach of sildenafil and tadalafil by investigating 1) theeffects of PDE5 inhibitors in vitro dilatation of the mid-dle cerebral artery (MCA) with controlled luminal orextra-luminal application of the drugs and 2) the in vivoeffects of intravenous PDE5 inhibitors on the middlemeningeal artery (MMA) dilatation in a closed cranialwindow model in rats.MethodsRat MCA diameter was investigated using pressurisedarteriography, applying UK-114,542, sildenafil, andtadalafil intra- or extra-luminally. Effects on MMA werestudied in the in vivo closed cranial window model.ResultsAt high concentrations,…
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