Effects of adrenomedullin on vascular calcification in rats

Objective The aim of the present study was to investigate the effect of adrenomedullin (ADM) on vascular calcification. Methods The vascular calcification model was established in rats (VND group) by using vitamin D3 (300 000 IU/kg) and nicotine (25 mg/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 I-125-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 the VDN group was ob- viously increased; in addition ADM concentrations in plasma and vessels of rats in VDN group were increased. But the maximum binding sites of I-125-ADM for ADM receptor (Bmax) on vascular plasma membrane in rats of VDN group were significantly decreased compared with control rats. The affinity of I-125-ADM for the ADM receptor was reduced, as shown by the Kd value and vascular cAMP content being reduced in rats of the VDN group compared to the control group. The in vitro re-sponse of isolated vessels to ADM incubation 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 Bmax of I-125-ADM for ADM receptors on vascular plasma membrane increased by 17.7% (p<0.01), and the value of Kd decreased by 36.2% (P<0.01) in rats treated with ADM as compared with rats of the VDN group. In addition, the vascular cAMP content and the response to ADM in isolated aorta were markedly increased. Conclusion Vascular calcification induced an alteration of the vascular ADM-ADM receptorcAMP pathway. Treatment with exogenous ADM inhibited vascular calcification by improving the vascular ADM-ADM receptorcAMP pathway.Cardiac & Cardiovascular SystemsSCI(E)07568-5749