Effect of human adrenomedullin on a canine tibial perfusion model in the absence of vascular endothelium

The effect of human adrenomedullin was investigated using an ex vivo perfused canine tibial model in the absence of vascular endothelium. Adrenomedullin is a novel peptide with known vasodilator properties. In this model, a 0.1 ml bolus injection of 10^-5 M of either acetylcholine or adrenomedullin decreased vascular resistance in tibial preparations precontracted with prostaglandin F(2α) by 88.3 ± 3.0% and 92.8 ± 2.8%, respectively, in the presence of vascular endothelium. Conversely, a 0.1 ml bolus injection of 10^-5 M acetylcholine produced a constrictor response after removal of vascular endothelium. A 0.1 ml bolus injection of 10^-5 M adrenomedullin decreased the baseline perfusion pressure in a dose-dependent manner for a duration of 20 minutes and also attenuated the pressor response to exogenous norepinephrine injection for at least 10 minutes compared with the control study (p < 0.05) in the absence of vascular endothelium. These data suggest that human adrenomedullin relaxes blood vessels in bone by a direct action on vascular smooth-muscle cells. In addition, the attenuation effect of human adrenomedullin on pressor responses to exogenous norepinephrine injection is independent of vascular endothelium.