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 125I-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 obviously increased; in addition ADM concentrations in plasma and vessels of rats in VDN group were increased. But the maximum binding sites of 125I-ADM for ADM receptor (Bmax) on vascular plasma membrane in rats of VDN group were significantly decreased compared with control rats. The affinity of 125I-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 response 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 125I-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.


CONCLUSIONS
Vascular calcification induced an alteration of the vascular ADM-ADM receptor-cAMP pathway. Treatment with exogenous ADM inhibited vascular calcification by improving the vascular ADM-ADM receptor-cAMP pathway.
Zhang
B
B
Department of Pediatrics, First Hospital, Peking University, Beijing 100034, P.R. China.
Tang
C
C
Jiang
Z
Z
Qi
Y
Y
Pang
Y
Y
Du
J
J
D053607:Adrenomedullin; D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D001013:Aorta, Thoracic / Q000473:pathology; D001018:Aortic Diseases / Q000473:pathology*; D001161:Arteriosclerosis / Q000473:pathology*; D002114:Calcinosis / Q000473:pathology*; D002118:Calcium / Q000378:metabolism; D046508:Culture Techniques; D000242:Cyclic AMP / Q000378:metabolism; D004195:Disease Models, Animal; D008081:Liposomes; D008297:Male; D009206:Myocardium / Q000473:pathology; D010455:Peptides / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D058265:Receptors, Adrenomedullin; D018000:Receptors, Peptide / Q000378:metabolism
D008081:Liposomes; D010455:Peptides; D058265:Receptors, Adrenomedullin; D018000:Receptors, Peptide; D053607:Adrenomedullin; D000242:Cyclic AMP; D000469:Alkaline Phosphatase; D002118:Calcium