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 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.
Lambert
Geoffrey Andrew
GA
Institute of Neurological Sciences, Room G39, Clinical Sciences Building, The Prince Henry and Prince of Wales Hospitals and School of Medicine, University of New South Wales, 2031 Randwick, NSW, Australia. G.Lambert@unsw.edu.au
Donaldson
Cathy
C
Hoskin
Karen Lisa
KL
Boers
Peter Michael
PM
Zagami
Alessandro Stefano
AS
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002415:Cats; D004106:Dilatation; D005730:Ganglionic Blockers / Q000494:pharmacology; D018738:Hexamethonium / Q000494:pharmacology; D007269:Injections, Intra-Arterial; D007275:Injections, Intravenous; D008576:Meningeal Arteries / Q000187:drug effects* / Q000502:physiology; D011985:Receptors, Serotonin / Q000378:metabolism*; D012039:Regional Blood Flow / Q000187:drug effects; D012701:Serotonin / Q000008:administration & dosage / Q000494:pharmacology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D014628:Vagotomy; D014655:Vascular Resistance / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology*
D005730:Ganglionic Blockers; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D014665:Vasodilator Agents; D012701:Serotonin; D018738:Hexamethonium