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

Abstract

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 microg 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-HT1A antagonist), GR127935 (5-HT(1B/1D) antagonist), methiothepin (5-HT2C and 5-HT7 antagonist), ketanserin (5-HT2A 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.

Serotonergic mechanisms of trigeminal meningeal nociception: Implications for migraine pain

“…Accordingly, functional elimination of the 5-HT3 receptor reduces tissue injury-induced nociception in mice (Zeitz et al, 2002). 5-HT3 receptors are also involved in vasodilation induced by 5-HT in duramater (Lambert et al, 2004). Here we show that 5-HT3 receptors in meningeal fibers mediate also release of the neuropeptide CGRP, a Version: Postprint (identical content as published paper) This is a self-archived document from i3S -Instituto de Investigação e Inovação em Saúde in the University of Porto Open Repository For Open Access to more of our publications, please visit http://repositorio-aberto.up.pt/ A01/00 principal trigger of migraine, which may cause neurogenic inflammation and migraine headache.…”

“…Our results suggest that 5-HT released from dural mast cells (Levy, 2009;Tore and Tuncel, 2011) and/or aggregated platelets (Taffi et al, 2005) induces nociceptive firing in nerve terminals. The effect can become long-lasting due to contributing vasodilation (Lambert et al, 2004), extravasation (Williamson et al, 1997) and neuro-inflammation triggered by multiple pro-inflammatory compounds, including ATP (Yegutkin et al, 2016) and CGRP (Markowitz et al, 1987;Fabbretti et al, 2006). However, activation of the peripheral meningeal nerve endings by 5-HT could be counterbalanced, by its inhibitory action on the central terminals synapsing on lamina I neurons in the brainstem and upper cervical spinal cord.…”