ADRENOMEDULLIN-(22-52) ANTAGONIZES VASODILATOR RESPONSES TO CGRP BUT NOT ADRENOMEDULLIN IN THE CAT

The effects of adrenomedullin (ADM)-(22-52), a putative ADM receptor a ntagonist, on vasodilator responses to ADM and the structurally relate d peptide, calcitonin gene-related peptide (CGRP), were investigated i n the hindlimb vascular bed of the cat under constant-flow conditions. ADM-(22-52) had no significant effect on hindlimb perfusion pressure when injected in doses up to 120 nmol; after administration of ADM-(22 -52), vasodilator responses to ADM were unchanged, whereas vasodilator responses to CGRP were inhibited. The inhibitory effects of ADM-(22-5 2) on responses to CGRP were selective and reversible and were similar to the inhibitory effects of the CGRP antagonist CGRP-(8-37). Hindlim b vasodilator responses to CGRP and to ADM were increased in duration by the adenosine 3',5'-cyclic monophosphate (cAMP) phosphodiesterase i nhibitor rolipram but were not altered by inhibitors of guanosine 3',5 '-cyclic monophosphate phosphodiesterase, nitric oxide synthetase, K+- ATP channels, the cyclooxygenase pathway, or the adrenergic nervous sy stem. These results demonstrate that ADM-(22-52) is a selective CGRP r eceptor antagonist in the hindlimb vascular bed of the cat. The presen t data suggest that vasodilator responses to CGRP and ADM are mediated by different receptors but that these peptides dilate the hindlimb va scular bed of the cat by a similar cAMP-dependent mechanism.