An ex vivo model of a perfused canine tibia was used to investigate the effect of human adrenomedullin, a novel peptide with known vasodilator properties, on the vascular resistance of bone. Human adrenomedullin has a potent and long-lasting vasodilator effect in the canine tibia following precontraction of vascular smooth muscle by infusion of prostaglandin F2 alpha. A 0.1 ml bolus injection of 10(-5) M human adrenomedullin suppressed the pressor response of the canine tibia preparation to an infusion of norepinephrine by 43-52% for a duration of 100 minutes. An injection of 10(-6) adrenomedullin suppressed the pressor response to an infusion of norepinephrine by 22-23% for a duration of 40 minutes. These data suggest that human adrenomedullin may be a potent and long-acting vascular smooth-muscle relaxant in bone.