The calcitonin gene-related peptide (CGRP) antagonist CGRP(8-37) blocks vasodilatation in inflamed rat skin: involvement of adrenomedullin in addition to CGRP

The neuropeptide calcitonin gene-related peptide (CGRP) is a potent microva scular vasodilator in rat skin and effects are antagonised by CGRP(8-37), I n this study, CGRP(8-37) significantly (P < 0.05) inhibited the time-depend ent (3-5 h) increase in skin blood flow measured in the anaesthetised rat, after intradermal administration of the inflammatory cytokine interleukin-1 beta (3 pmol/site), indicating the involvement of CGRP1 receptors. The CGR P-related peptide adrenomedullin (ADM) is also a potent vasodilator in rat skin,with effects antagonised by CGRP(8-37) We show that ADM mRNA expressio n is increased in rat skin after treatment with IL-1 beta and that the IL-1 p-induced blood flow is blocked by a selective ADM antibody (P < 0.05). Thu s ADM is expressed locally in the inflamed cutaneous microvasculature where it can, in addition to, or as an alternative to CGRP, contribute to IL-1 b eta -induced vasoactive effects. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.