SUMATRIPTAN INHIBITS NEUROGENIC VASODILATION OF DURAL BLOOD-VESSELS IN THE ANESTHETIZED RAT - INTRAVITAL MICROSCOPE STUDIES

This study used intravital microscopy to measure the diameter of dural arteries in anaesthetized rats. Electrical stimulation of the surface of a closed cranial window produced increases in dural vessel diamete r which were blocked by the CGRP receptor antagonist human-alpha CGRP( (8-37)) but unaffected by the NK1 receptor antagonist RP67580. Sumatri ptan (3 and 10 mg kg(-1), iv) significantly reduced the response to el ectrical stimulation. In contrast, sumatriptan (3 mg kg(-1)) had no ef fects on the response to exogenously administered CGRP. These results indicate that neurokinins play no role in neurogenic vasodilation in t his preparation and that neurogenic vasodilation in rat dural vessels is mediated predominantly by CGRP. Furthermore, the data indicate that sumatriptan attenuates neurogenic vasodilation, probably by inhibitin g the release of CGRP from perivascular trigeminal nerve endings inner vating the dura. These experimental data parallel the clinical finding s that CGRP levels are elevated in migraine and normalized, concomitan tly with headache relief, by sumatriptan.