EFFECTS OF THE 5-HT1 RECEPTOR AGONISTS, SUMATRIPTAN AND CP-93,129, ONDURAL ARTERIAL FLOW IN THE RAT

The blood flow in and around the medial meningeal artery (dural arteri al flow) was recorded in the exposed parietal dura mater encephali of the anesthetized rat using laser Doppler flowmetry. Local electrical s timulation of the dura mater (pulses of 0.5 ms delivered at 7.5-17.5 V and 5 or 10 Hz for 30 a) caused temporary increases in dural arterial flow. The effects of the 5-HT1 receptor agonists sumatriptan and CP 9 3,129 on the basal flow and the electrically evoked increases in flow were examined. Topical administration of undiluted sumatriptan (12 mg/ ml) lowered the basal and the evoked flow by 20% on average. Systemic (i.v.) administration of sumatriptan (0.24, 0.72 and 3.6 mu mol/kg) ca used a short-lasting reduction of the evoked flow increases only at th e higher doses while the basal flow was not significantly altered. Sys temic administration of CP 93,129 (0.46 and 4.6 mu mol/kg) caused no s ignificant changes of the basal and the evoked flow. At a dose of 23 m u mol/kg CP 93,129 lowered the basal flow by 20% and the evoked flow b y 30% for 20 min. The systemic arterial pressure was not significantly attend by sumatriptan and CP 93,129 within the whole range of doses. It is suggested that sumatriptan and CP 93,129 at high doses exert inh ibitory effects on those fine afferent nerve fibers which release the calcitonin gene-related peptide, since this neuropeptide mediates the evoked increases in dural arterial flow. (C) 1997 Elsevier Science B.V .