肾上腺髓质素对大鼠血管钙化的影响

目的　观察肾上腺髓质素 (ADM)对血管钙化的影响。方法　维生素D3 (VitD3 )和尼古丁制备大鼠血管钙化模型 ,分别测定血管、心肌钙含量和血管碱性磷酸酶 (ALP)活性 ,血浆和血管ADM含量 ,12 5I ADM与ADM受体的结合力及血管环磷酸腺苷 (cAMP)含量。结果　与对照组相比 ,钙化组 (VDN组 )的血管钙含量和ALP活性明显升高 ;血管及血浆ADM的含量亦升高 ,但12 5I ADM与血管质膜ADM受体结合的位点减少 ,Kd值升高 ,提示亲合力降低 ,同时伴钙化血管的cAMP合成减少。提示钙化血管对ADM的反应减弱。空载脂质体对血管钙化无影响。用脂质体包裹ADM组 (VDN ADM组 )与钙化组相比 ,其血管的钙含量、ALP的活性均明显降低 ;12 5　I ADM与血管质膜ADM受体结合的位点增加 ,Kd值减少 ,cAMP的合成也增加 ,提示该组血管对ADM的反应增强。结论　血管钙化时ADM ADM受体 cAMP途径发生变化 ,外源性ADM通过改善ADM ADM受体 cAMP途径 ,发挥抑制血管钙化的作用

Effects of adrenomedullin on vascular calcification in rats

Objective To investigate the effect of adrenomedullin (ADM) on vascular calcification. Methods Vascular calcification model was established in rats (VDN group) by using vitamin D 3 (300kU/kg) and nicotine (25mg/kg, two doses). The effect of liposome encapsulated ADM was observed. Vascular calcium content, alkaline phosphatase (ALP) activity, ADM in aortic tissue and plasma, binding ability of 125 I ADM for ADM receptor on vascular plasma membrane and content of cAMP in vessels were measured.Results Compared with control rats, the aortic calcium content and vascular ALP activity in rats of VDN group were obviously increased, also ADM concentrations in plasma and vessels of rats in VDN group were increased. But the maximum binding sites of 125 I ADM for ADM receptor (B max ) on vascular plasma membrane in rats of VDN group were significantly decreased as compared with control rats. The affinity of 125 I ADM for ADM receptor was reduced as shown by increased Kd value, and reduced vascular cAMP content in rats of VDN group compared with control one. The in vitro response of isolated vessels to ADM was weakened. Administration of empty liposome had no effect on vascular calcification. But administration of ADM significantly decreased vascular calcium content and ALP activity. The B max of 125 I ADM for ADM receptors on vascular plasma membrane increased and the value of Kd decreased in rats treated with ADM compared with rats of VDN group. In addition, the vascular cAMP content and the response to ADM in isolated aorta were markedly increased. Conclusions Vascular calcification induced an alternation of vascular ADM ADM receptor cAMP pathway. Treatment with exogenous ADM inhibited vascular calcification by improving vascular ADM ADM receptor cAMP pathway.