Vasopressor activities of N-terminal fragments of adrenomedullin in anesthetized rat

Adrenomedullin (AM) is a vasorelaxant peptide that was recently isolated from human pheochromocytoma, In contrast to human (h) AM, which has vasodepressor activity, a synthetic N-terminal fragment of hAM, hAM-(1-25)-NH2 showed vasopressor activity in the anesthetized rat. The N-terminal peptides hAM-(1-31)-NH2, hAM-(1-25)-OH, hAM-(1-21)-NH2, acetyl-hAM-(16-21)-NH2, and acetyl-hAM-(16-36)-OH all showed vasopressor activities. The potency of hAM-(1-21)-NH2, acetyl-hAM-(16-21)-NH2 was greater than that of hAM-(1-25)-NH2. Pretreatment with phenoxybenzamine, guanethidine or reserpine attenuated vasopressor activities of these peptides. These data suggested that vasopressor activity of N-terminal fragment of hAM is due to a stimulation of endogenous catecholamine release. (C) 1996 Academic Press, Inc.