Dilatation induced by 5-HT in the middle meningeal artery of the anaesthetised cat

In chloralose-anaesthetised cats, we studied the effects of intravenous and intra-carotid injections of 5-HT on the middle meningeal artery and the way these were modified by 5-HT antagonists. Cats were prepared for blood pressure recording and intravenous injections and a catheter inserted into one carotid artery via a lingual artery. The middle meningeal arteries were exposed and blood flow recorded with laser Doppler probes. Intravenous injections of 5-HT, 2–50 µg kg^–1 (5.2–129 nmole kg^–1), produced a dose-dependent fall in blood pressure, a rise in meningeal blood flow, and an associated fall in middle meningeal resistance. Resistance changes were the result of a local dilatation and not due to changes downstream of the recording probe. Intracarotid injections of 5-HT produced similar systemic and craniovascular responses, which were larger in the ipsilateral middle meningeal artery. Dose-response curves of vascular resistance changes to intravenous injection of 5-HT were not significantly affected by WAY100635 (5-HT_1A antagonist), GR127935 (5-HT_1B/1D antagonist), methiothepin (5-HT_2C and 5-HT₇ antagonist), ketanserin (5-HT_2A antagonist), SB203186 (5-HT₄ antagonist) or cervical sympathectomy, but were blocked by the 5-HT_3/4 antagonist tropisetron, the 5-HT₃ antagonist ondansetron, the ganglion-blocking drug hexamethonium and by vagotomy. These drugs and procedures did not significantly antagonise the response to intra-arterially injected 5-HT. We conclude that intravenously-administered 5-HT is a vasodilator in vivo in the cat dural circulation, and that the dilation is not mediated by 5-HT₁, 5-HT₂, 5-HT₄ or 5-HT₇ receptors, but is primarily mediated by a vagal reflex, initiated via 5-HT₃ receptor activation and brought about by an increase in parasympathetic tone to the middle meningeal artery as part of the von Bezold-Jarisch reflex. There also appears to be a direct vasodilator effect mediated by unknown receptor types, particularly after intra-arterial administration. Neither of these effects is, however, likely to be of importance in the pathophysiology of migraine or other vascular headaches.