As N type calcium channel blockade in addition to L type calcium channel blockade by cilnidipine elicited the greater suppression of the podocyte harm and the proteinuria than the inhibition of L type calcium channel by amlodipine, it could be considered that the inhibition Fostamatinib molecular weight of N type calcium channel by cilnidipine in podocyte may possibly stop the podocyte injury and cause the antiproteinuric exercise of cilnidipine in SHR/ND. AngII triggers superoxide production by activating NADPH oxidase in several tissues including kidney and is implicated in the improvement of proteinuria and renal injury in experimental hypertensive or diabetic subjects. Furthermore, AngII improved NADPH oxidase superoxide generation and activity, subunits expression and altered the phenotype of podocyte cytoskeleton by reactive oxygen species in cultured murine podocytes, suggesting that AngII might encourage oxidative stress and produce podocyte injury, thus accelerating proteinuria. Actually, in the present study, both increased renal AngII amounts and oxidative stress were observed in SHR/ND, which were accompanied by podocyte injury and proteinuria. Moreover, treatment with cilnidipine, but not with amlodipine, somewhat suppressed these Chromoblastomycosis changes. These studies suggest that cilnidipine, independent of its hypotensive effect, elicits podocyte safety and antiproteinuric effect in SHR/ND through a subsequent reduction in oxidative stress and the reduction of AngII. A limitation of the current study is that we couldn’t directly assess the changes in the AngII levels and oxidative stress in podocytes of SHR/ND due to the technical constraints on quantitative analysis in vivo. But, the in vitro results that showed D type calcium-channel dependent superoxide production by AngII could partially support our theory. Furthermore, we recently noted that cilnidipine had tougher antioxidant action than amlodipine in vitro. Therefore, cilnidipine may engage Canagliflozin SGLT Inhibitors in the further reduction of AngII induced oxidative stress through the inhibitory effect of N type calcium channel and its direct antioxidative effect in podocytes, although the mechanism where cilnidipine suppressed AngII level in vivo still remains unclear in the present study. An L type calcium-channel blocker, amlodipine, initially suppressed proteinuria in SHR/ND, however, it reached levels comparable to those at week 34. Furthermore, amlodipine didn’t restore the reduction of nephrin and podocin appearance and, somewhat, increased the desmin discoloration, indicating that amlodipine has no protective influence on podocytes. It’s also possible that the original antiproteinuric effect of amlodipine results from the blood pressure lowering effect. Indeed, many studies have noted that the changes in intracellular calcium concentration, an important biological role of calcium channel, in response to AngII, catecholamine and acetylcholine, weren’t inhibited by L type CCBs in podocytes, indicating that L type calcium channel may not play important roles in podocytes.