Inhibition by adrenomedullin of amine release from adrenergic nerves in dog mesenteric arteries

Adrenomedullin and calcitonin gene-related peptide (CGRP) inhibited the pre sser response to transmural electrical stimulation in perfused isolated can ine mesenteric arteries. The response was abolished by treatment with eithe r prazosin or tetrodotoxin. Adrenomedullin-(22-52), an adrenomedullin recep tor antagonist, reduced the inhibitory effect of adrenomedullin (10(-10) to 10(-8) mol/l), but did not alter the action of CGRP. CGRP-(8-37), a CGRP(1 ) receptor antagonist, did not affect the inhibition induced by adrenomedul lin, but reversed the CGRP-induced inhibition, in helical strips of the art eries, adrenomedullin (up to 10(-8) mol/l) did not influence the contractio n induced by noradrenaline, whereas CGRP attenuated the response. Adrenomed ullin decreased the release of noradrenaline from adrenergic nerves elicite d by transmural electrical stimulation, but CGRP had no effect. Adrenomedul lin-(22-52) reversed the decrease in noradrenaline release induced by adren omedullin. The adrenomedullin-induced relaxation of vascular strips precont racted with prostaglandin F-2 alpha was suppressed by CGRP-(8-37) but was u naffected by adrenomedullin-(22-52). These findings suggest that adrenomedu llin impairs noradrenaline release from adrenergic nerves by acting on adre nomedullin receptors located in the nerve terminals, whereas arterial relax ation caused by adrenomedullin and CGRP is due to activation of CGRP(1) rec eptors in vascular smooth muscle. (C) 1999 Elsevier Science B.V. All rights reserved.