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

Journal of Orthopaedic Research : Official Publication of the Orthopaedic Research Society
T KatoM B Wood

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.

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Citations

Mar 16, 2007·Proceedings of the National Academy of Sciences of the United States of America·Kathleen CaronOliver Smithies
Oct 7, 2004·Pharmacology & Therapeutics·David C BuntonJohn J V McMurray
Oct 21, 2006·Molecular Endocrinology·Carrie GibbonsKathleen M Caron

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