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.
ASJC Scopus subject areas
- Orthopedics and Sports Medicine