EFFECTS OF HCGRP-8-37 AND THE NK1-RECEPTOR ANTAGONIST SR-140.333 ON CAPSAICIN-EVOKED VASODILATION IN THE PIG NASAL-MUCOSA IN-VIVO

A novel pig in vivo model was used to study vascular effects of capsai cin. substance P and calcitonin gene-related peptide (CGRP) in the nas al mucosa and skin. An acoustic rhinometer was used to measure changes in nasal cavity volume. mainly representing changes in capacitance ve ssels in the vascular beds, The non-peptide NK1-receptor antagonist SR 140.333 and the CGRP-receptor antagonist hCGRP 8-37 were used to inve stigate the role of substance P and CGRP. respectively. in capsaicin-e voked vasodilation mediated through activation of sensory C-fibre affe rents. In this study we show that SR 140.333 is a potent inhibitor of substance P-induced vasodilation in the nasal mucosa whereas it has no effect on the capsaicin-evoked responses. Substance P only elicited a minor and shortlasting increase in superficial skin blood flow. this response. however. was completely blocked after administration of SR 1 40.333. Capsaicin-evoked vasodilation in the skin was slightly reduced by SR 140.333, CGRP-induced vasodilation in the nasal mucosa and skin was of much longer duration than the substance P-induced response, an d was thus similar to the vascular effects mediated by capsaicin. hCGR P 8-37 significantly reduced both the CGRP- and capsaicin-mediated vas odilation in the nasal mucosa and the decrease of nasal cavity volume. Although the peak vasodilation in the skin in response to capsaicin. was unaltered by blockade oi CGRP-receptors. the integrated response w as significantly reduced by hCGRP 8-37. The present results show that vasodilatory responses to activation of afferent nerves in the pig nas al mucosa and superficial skin are mainly dependent on CGRP. while NK1 -receptor mechanisms seem to be of no or minor importance.