Neurogenic vasodilation in rabbit basilar isolated artery: involvement of calcitonin-gene related peptide

Neurogenic vasodilation in cranial arteries may be an important mechanism in the pathogenesis of migraine headache. We describe a novel, in vitro assay to characterise neurogenic vasodilator responses in endothelium-denuded segments of rabbit isolated basilar artery, with particular focus on calcitonin-gene related peptide (CGRP). In arterial segments precontracted with prostaglandin F(2alpha), relaxations evoked by exogenously applied alphaCGRP (EC(50)=2.9 nM) were inhibited by alphaCGRP-(8-37) (pA(2)=6.49) or by desensitisation resulting from prior exposure to alphaCGRP. Relaxations evoked by exogenously applied vasoactive intestinal polypeptide (VIP) (EC(50)=2.5 nM) were inhibited by VIP-(7-28) 1 microM. The 5-HT(1) receptor agonists L-771,331 ((3S)-3[N-(S)-alpha-methylbenzyl]aminomethyl-(S)-1-[2-(5-(2-oxo-1, 3-oxazolidin-4-ylmethyl)-1H-indol-3-yl)ethyl]pyrrolidine) and sumatriptan exerted contractile effects (EC(50)=293 and 95 nM, respectively). In neurogenic experiments, vasodilation evoked by electrical field stimulation was markedly attenuated by pre-treatment with capsaicin (10 microM) or by prior CGRP receptor desensitisation and to a lesser extent by pre-treatment with VIP-(7-28) 1 microM. 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 alphaCGRP-(8-37) 1 microM (reversible on wash-out). Short application (5-10 min) of capsaicin (10 microM) produced vasodilation that was inhibited by alphaCGRP-(8-37) 1 microM. These data suggest that electrically evoked neurogenic 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.