THE INVOLVEMENT OF CALCITONIN-GENE-RELATED PEPTIDE (CGRP) AND SUBSTANCE-P IN FELINE PIAL ARTERY DIAMETER RESPONSES EVOKED BY CAPSAICIN

The effects of capsaicin and selective neuropeptide antagonists on pia l artery diameter were measured using an on-line image analyser in ana esthetised cats, in order to monitor the effects of mediators released in response to activation of trigeminal nerves. Perivascular injectio n of CGRP (10(-8) M) and the neurokinin-1 (NK1) receptor agonist subst ance P methyl ester, SPOMe (10(-6) M) produced an increase in pial art ery diameter. The vasodilatory action of these agonists was significan tly and selectively inhibited using the CGRP receptor antagonist, CGRP (8-37) (10(-6) M), and the NK1 receptor antagonist, CP99994 (10(-6) M) respectively. Capsaicin (10(-8)-10(-5) M) produced a biphasic respons e upon perivascular injection that was concentration dependent. At 10( -6) M capsaicin an initial transient vasoconstriction was observed fol lowed by a longer-lasting vasodilatation. The vasodilator component wa s significantly reduced by CGRP(8-37) (10(-6) M) or CP99994 (10(-6) M) . These results show that chemical (capsaicin) activation of trigemina l nerves leads to vasodilatation of feline arteries in situ. This vaso dilatation is mediated via the activation of CGRP and NK1 receptors pr obably via the efferent release of CGRP and a substance P-like peptide .