Objective To examine whether the two vascular paracrine/autocrine factors,angiotensin Ⅱ(Ang Ⅱ)andendothelin,participate in the pathogenesis of arterial calcification.Methods Nicotine and vitamin D_3 treated ratswere studied.Vascular calcification was confirmed by using Von Kossa staining,measurement of calcium content,~(45)Ca~(2+)uptake assay and alkaline phosphatase(ALP)activity.The plasma and vascular Ang Ⅱ and endothelin levelswere measured by using radioimmunoassay.Angiotensinngen and endothehn mRNA levels were determined by RT-PCR.Results The arterial calcium content,~(45)Ca~(2+)uptake and ALP activity were increased in calcification groupscompared with control(P<0.01).Administration of the angiotensin receptor antagonist losartan,the endothelinreceptor antagonist bosentan,and the angiotensin-converting enzyme inhibitor captopril reduced significantly thearterial calcium content,~(45)Ca~(2+)uptake and ALP activity.In addition,the plasma and aortic Ang Ⅱ and endothelincontents,and vascular angiotensinngen and endothelin mRNA expression were significantly up-regulated(P<0.05).Conclusions These findings suggest that functional renin-angiotensin system and endothelin pathway are involved invascular calcification,and that activation of these systems could potentiate pathogenesis of arterial calcification.(JGeriatr Cardiol 2004;1(2):108-113.) Objective To examine whether the two vascular paracrine / autocrine factors, angiotensin Ⅱ (Ang Ⅱ) andendothelin, participate in the pathogenesis of arterial calcification. Methods Nicotine and vitamin D_3 treated rats were studied. Vascular calcification was confirmed by using Von Kossa staining, measurement of calcium content, ~ (45) Ca ~ (2 +) uptake assay and alkaline phosphatase (ALP) activity.The plasma and vascular Ang Ⅱ and endothelin levels were measured by using radioimmunoassay.Angiotensin mRNA and endothehn mRNA levels were determined by RT-PCR. Results The The arterial calcium content, ~ (45) Ca ~ (2 +) uptake and ALP activity were increased in calcification groups compared with control (P <0.01) .Administration of the angiotensin receptor antagonist losartan, the endothelin receptor antagonist bosentan, and the angiotensin-converting enzyme Inhibitor captopril reduced significantly thearterial calcium content, ~ (45) Ca ~ (2 +) uptake and ALP activity.In addition, the plasma and aortic Ang ¢ ò and endothelinconte nts, ​​and vascular angiotensin gene and endothelin mRNA expression were significantly up-regulated (P <0.05) .Conclusions These results suggest that functional renin-angiotensin system and endothelin pathway are involved in invascular calcification, and that activation of these systems could potentiate pathogenesis of arterial calcification (JGeriatr Cardiol 2004; 1 (2): 108-113.)