Adrenergic modulation of calcitonin gene-related peptide (CGRP)-containing nerve-mediated vasodilation in the rat mesenteric resistance vessel.

Pharmacological studies showed that periarterial nerve stimulation (PNS) of the perfused rat mesenteric vascular bed contracted with endothelin, a vasoconstrictor peptide, in the presence of prazosin (alpha 1-adrenoceptor antagonist) produced a frequency-dependent neurogenic vasodilation when the adrenergic neurotransmission was blocked by the adrenergic neuron blocker, guanethidine. The PNS-evoked vasodilation was attenuated by tetrodotoxin and capsaicin treatment, and was also inhibited when the adrenergic neurotransmitter (norepinephrine; NE) release was left intact in the absence of guanethidine. However, in the combined presence of an alpha 2-adrenoceptor antagonist (yohimbine) and prazosin, PNS caused a marked neurogenic vasodilation even when the neuronal release of NE was left intact. These results suggest that NE released from adrenergic nerves regulates the release of a vasodilator substance, CGRP, through activation of alpha 2-adrenoceptors on CGRP-containing vasodilator nerves.