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

Abstract

Adrenomedullin and calcitonin gene-related peptide (CGRP) inhibited the pressor response to transmural electrical stimulation in perfused isolated canine mesenteric arteries. The response was abolished by treatment with either prazosin or tetrodotoxin. Adrenomedullin-(22-52), an adrenomedullin receptor 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 adrenomedullin, but reversed the CGRP-induced inhibition. In helical strips of the arteries, adrenomedullin (up to 10(-8) mol/l) did not influence the contraction induced by noradrenaline, whereas CGRP attenuated the response. Adrenomedullin decreased the release of noradrenaline from adrenergic nerves elicited by transmural electrical stimulation, but CGRP had no effect. Adrenomedullin-(22-52) reversed the decrease in noradrenaline release induced by adrenomedullin. The adrenomedullin-induced relaxation of vascular strips precontracted with prostaglandin F(2alpha) was suppressed by CGRP-(8-37) but was unaffected by adrenomedullin-(22-52). These findings suggest that adrenomedullin impairs noradrenaline release from adrenergic nerves by acting on adrenomedullin receptors located in the nerve terminals, whereas arterial relaxation caused by adrenomedullin and CGRP is due to activation of CGRP(1) receptors in vascular smooth muscle.