title: Effect of human adrenomedullin on a canine tibial perfusion model in the absence of vascular endothelium.
abstract: 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 F2 alpha 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.
authors.affiliation: Department of Orthopedics, Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: T
authors.initials: T
authors.lastname: Kato
authors.forename: A T
authors.initials: AT
authors.lastname: Bishop
authors.forename: M B
authors.initials: MB
authors.lastname: Wood
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D053607:Adrenomedullin; D000818:Animals; D001808:Blood Vessels / Q000187:drug effects; D015237:Dinoprost / Q000494:pharmacology; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000502:physiology*; D005260:Female; D006801:Humans; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology*; D010477:Perfusion; D013977:Tibia / Q000098:blood supply*; D013997:Time Factors; D014655:Vascular Resistance / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: D010455:Peptides; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D053607:Adrenomedullin; D015237:Dinoprost; D000109:Acetylcholine; D009638:Norepinephrine