SENSORY NERVES, NITRIC-OXIDE AND NANC VASODILATATION

Primary afferent neurons, originating from the dorsal root ganglia, pr ovide a perivascular network of fibres around the arterial system thro ughout the body. When stimulated, these fibres cause a nonadrenergic n oncholinergic (NANC) vasodilatation by release of calcitonin gene-rela ted peptide (CGRP). This peptide is a potent vasodilator and, in this action, cooperates with nitric oxide (NO) in a tissue-specific manner. The hyperaemic effect of intravascularly injected rat CGRP-alpha in t he rat gastric mucosa is reduced by blockade of the NO synthesis, whic h indicates that CGRP dilates the gastric microvascular bed via NO-dep endent and -independent mechanisms. This is also true for endogenous C GRP, as the gastric mucosal hyperaemia, which is caused by gastric aci d challenge and involves CGRP, is likewise blocked by inhibition of th e NO synthesis. The CGRP/NO-mediated vasodilatation is an important el ement of a neural emergency system that strengthens the resistance of the gastric mucosa in the face of pending acid injury. In the rat skin , CGRP participates in neurogenic inflammatory processes but the cutan eous vasodilator action of exogenous CGRP and the CGRP-mediated vasodi latation, evoked by antidromic stimulation of afferent nerve fibres, d o not depend on the formation of NO. This L-arginine-derived autacoid, however, plays a role ill the release of CGRP from afferent nerve fib res in the skin since it contributes to the CGRP-mediated vasodilator responses to chemical irritation or immunological challenge via interl eukin-lp. These data indicate that the type of interaction between CGR P and NO in causing a NANC vasodilatation varies with the vascular bed under study. Depending on the tissue, NO may facilitate the release o f CGRP from afferent nerve fibres or be a secondary vasorelaxant messe nger of the peptide.