Inhibition of angiotensin II and blockade of endothelin receptors reduce arterial calcification in rats

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 D3 treated rats were studied. Vascular calcification was confirmed by using Von Kossa staining, measurement of calcium content, 45Ca2+ uptake assay and alkaline phosphatase (ALP) activity. The plasma and vascular Ang II and endothelin levels were measured by using radioimmunoassay. Angiotensinogen and endothelin mRNA levels were determined by RT-PCR. Results The arterial calcium content, 45Ca2 + 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, 45Ca2+ uptake and ALP activity. In addition, the plasma and aortic Ang II and endothelin contents, and vascular angiotensinogen 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.