It is well established that renin-angiotensin system (RAS) is the major regulatory networkthat maintains blood pressure, fluid and electrolyte balance and the homeostasis of cardiovascular system.Most studies in the last decades centered on the pivotal members of RAS, that is, angiotensinⅡ (AngⅡ) and angiotensin converting enzyme (ACE). Recent identification of ACE-2, the homology of ACE,and the identification of the multiple products degraded from angiotensinⅠ, including AngⅢ, AngⅣ,Ang1 -9, Ang1 -7, Des-Asp-angiotensinⅠ(DAAⅠ), etc, have proved that AngⅡ is not the only bio-logical active compound of RAS. Peptides derived from angiotensinogen,that is, family of angiotensins,display independent and pleiotropic biological activitiesin vivo, and interact with each other both in me-tabolism pathway and the biologic effects. The imbalance of the network of angiotensin metabolites exhib-its significant pathophysiological role in cardiovascular disease.
Objective To examine whether the two vascular paracrine/autocrine factors,angiotensin Ⅱ(Ang Ⅱ)and endothelin,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.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 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 the arterial calcium content,^(45)Ca^(2+)uptake and ALP activity.In addition,the plasma and aortic Ang Ⅱ and endothelin contents,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 in vascular calcification,and that activation of these systems could potentiate pathogenesis of arterial calcification.(J Geriatr Cardiol 2004;1(2):108-113.)
Juxiang LI~1 Shengying WU~1 Chunshui PAN~2 Yongfen QI~2 Bin GENG~1 Xiuhna LIU~~(1,2) Chaoshu TANG~1 1 Department of Physiology and Pathophysiology,Peking University Health Science Center,Beijing 100083,China 2 Insitiute of Cardiovascular Research,Peking University First Hospital,Beijing 100034,China
