Adrenomedullin(27-52) inhibits vascular calcification in rats

Adrenomedullin (ADM) has the vasodilatory properties and involves in the pathogenesis of vascular calcification. ADM could be degraded into more than six fragments in the body, including ADM((27-52)), and we suppose the degrading fragments from ADM do the same bioactivities as derived peptides from proadrenomedullin. The present study carries forward by assessing the effects on vascular calcification of the systemic administration of ADM((27-52)). The rat vascular calcific model was replicated with vitamine D-3 and nicotine. ADM or/and ADM((27-52)) were systemically administrated with mini-osmotic pump beginning at seventh day after the model replication for 25 days. Vascular calcific nodules histomorphometry, vascular calcium content, vascular calcium uptake, alkaline phosphatase activity, and osteopontin-mRNA quantification in aorta were assessed. ADM limited 40.2% vascular calcific nodules (P < 0.01), did not effect on calcium content (P > 0.05), reduced 44.4% calcium uptake (P < 0.01), lowered 21.1% alkaline phosphatase activity (P < 0.01), and regulated 40.9% downwards osteopontin-mRNA expression (P < 0.01) in the aorta of rats with vascular calcification. ADM((27-52)) receded 32.0% vascular calcific nodules (P < 0.01), taken from 55.5% calcium content (P < 0.01), did not affect calcium uptake (P > 0.05), inhibited 22.5% alkaline phosphatase activity (P < 0.01), and restrained 21.9% osteopontin-mRNA expression (P < 0.01) in the aorta of rats with vascular calcification. Both of ADM and ADM((27-52)) did interact on vascular calcification each other. ADM could partially antagonize the effects of ADM((27-52)) in taking from calcium content (17.5%, P < 0.01) and in receding vascular calcific nodules (18.6%, P < 0.01). ADM could obviously enhance the action of ADM((27-52)) in inhibiting alkaline phosphatase activity (14.4%, P < 0.01) and in reducing calcium uptake (11.4%, P < 0.01). ADM((27-52)) could partially antagonize the effects of ADM on regulating downwards osteopontin-mRNA expression (17.0%. P < 0.01). It is concluded that ADM((27-52)) derived from ADM acts as an inhibitory agent on vascular calcification, with special mechanisms different from ADM derived from ADM progenitor molecule. (c) 2005 Elsevier B.V. All rights reserved.