T. Olivar et al., Neurogenic vasodilation in rabbit basilar isolated artery: involvement of calcitonin-gene related peptide, EUR J PHARM, 395(1), 2000, pp. 61-68
Neurogenic vasodilation in cranial arteries may be an important mechanism i
n the pathogenesis of migraine headache. We describe a novel, in vitro assa
y to characterise neurogenic vasodilator responses in endothelium-denuded s
egments of rabbit isolated basilar artery, with particular focus on calcito
nin-gene related peptide (CGRP). In arterial segments precontracted with pr
ostaglandin F-2 alpha, relaxations evoked by exogenously applied alpha CGRP
(EC50 = 2.9 nM) were inhibited by alpha CGRP-(8-37) (pA(2) = 6.49) or by d
esensitisation resulting from prior exposure to aCGRP. Relaxations evoked b
y exogenously applied vasoactive intestinal polypeptide (VIP) (EC50 = 2.5 n
M) were inhibited by VIP-(7-28) 1 mu M. The 5-HT1 receptor agonists L-771,3
31 ((3S)-3[N-(S)-alpha-methylbenzyl]aminomethyl-(S)-1-[2-(5-(2-oxo-1,3-oxaz
olidin-4-ylmethyl)-1H-indol-3-yl)ethyl]pyrrolidine) and sumatriptan exerted
contractile effects (EC50 = 293 and 95 nM, respectively). In neurogenic ex
periments, vasodilation evoked by electrical field stimulation was markedly
attenuated by pre-treatment with capsaicin (10 mu M) Or by prior CGRP rece
ptor desensitisation and to a lesser extent by pre-treatment with VIP-(7-28
) 1 mu M. L-771,331 (100 nM) exerted a weak inhibitory effect, marked only
by a short reduction in the recovery time (post-electrical stimulation) and
sumatriptan (30 nM) had no effect. The neurogenic response was potentiated
by alpha CGRP-(8-37) 1 mu M (reversible on wash-out). Shea application (5-
10 min) of capsaicin (10 mu M) produced vasodilation that was inhibited by
alpha CGRP-(8-37) 1 mu M. These data suggest that electrically evoked neuro
genic vasodilation in rabbit basilar artery has a large component resulting
from the release of sensory neuropeptides in particular CGRP and a smaller
component involving the release of VIP. (C) 2000 Elsevier Science B.V. All
rights reserved.