The novel findings of the present study are; 1) Aortic expression of PRR and prorenin/renin was increased in CKD rats, whereas AST-120 reduced their expression; 2) IS increased aortic expression of PRR and prorenin/renin in rats; 3) IS increased expression of PRR and prorenin through OAT3, ROS, AhR and NF-κB in vascular smooth muscle cells; 4) IS-induced PRR activation is involved in vascular smooth muscle cell proliferation; 5) IS-induced PRR activation is involved in tissue factor expression in vascular smooth muscle cells. Here, REN is linked to chronic kidney disease.