Endothelium-dependent relaxant responses to selective 5-HT(1B/1D) receptor agonists in the isolated middle cerebral artery of the rat.
The vasomotor effects of triptans in the middle cerebral artery (MCA) of rats were studied using the pressurised arteriography method and in vitro vessel baths. Using the arteriograph, MCAs from Sprague-Dawley rats were mounted on two glass micropipettes, pressurised to 85 mm Hg and luminally perfused. Luminally added 5- hydroxytryptamine (5-HT), sumatriptan and rizatriptan induced maximal dilatations of 22 +/- 4, 10 +/- 2 and 13 +/- 5%, respectively, compared to the resting diameter. The relaxant effect of sumatriptan was blocked by the 5- HT(1B/1D) receptor selective antagonist GR 55562 (10(-6)M). The use of N(omega)-nitro-L-arginine and charybdotoxin revealed that the dilatation involved both nitric oxide and endothelially derived hyperpolarising factor. Thus, the earlier demonstrated expression of 5-HT(1B/1D) immunoreactivity in the endothelium may well translate into a relaxant response to 5-HT and triptans. Using the vessel bath technique, MCA segments were mounted on two metal wires. The relaxant responses to sumatriptan could not be reproduced using this model; instead, weak contractile responses (6 +/- 3% of submaximal contractile capacity) were observed. The difference in observations between the experimental models may be related to the maintenance of shear stress in the arteriograph.
Hansen-Schwartz
Jacob
J
Department of Internal Medicine, University Hospital of Lund, Lund, Sweden.
Løvland Hoel
Natalie
N
Nilsson
Elisabeth
E
Tfelt-Hansen
Peer
P
Edvinsson
Lars
L
D000818:Animals; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D020768:Middle Cerebral Artery / Q000187:drug effects* / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D058825:Serotonin 5-HT1 Receptor Agonists; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D018170:Sumatriptan / Q000494:pharmacology*; D014230:Triazoles / Q000494:pharmacology; D014363:Tryptamines; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology
D058825:Serotonin 5-HT1 Receptor Agonists; D017366:Serotonin Receptor Agonists; D014230:Triazoles; D014363:Tryptamines; C093622:rizatriptan; D018170:Sumatriptan